Amide substituted imidazoquinolines

ABSTRACT

Imidazoquinoline and tetrahydroimidazoquinoline compounds that contain amide functionality at the 1-position are useful as immune response modifiers. The compounds and compositions of the invention can induce the biosynthesis of various cytokines and are useful in the treatment of a variety of conditions including viral diseases and neoplastic diseases.

This is a continuation of Application No. 60/138,365 filed Jun. 10,1999.

FIELD OF THE INVENTION

This invention relates to imidazoquinoline compounds that have an amidecontaining substituent at the 1-position, and to pharmaceuticalcompositions containing such compounds. A further aspect of thisinvention relates to the use of these compounds as immunomodulators, forinducing cytokine biosynthesis in animals, and in the treatment ofdiseases, including viral and neoplastic diseases.

BACKGROUND OF THE INVENTION

The first reliable report on the 1H-imidazo[4,5-c]quinoline ring system,Backman et al., J. Org. Chem. 15, 1278-1284 (1950) describes thesynthesis of1-(6-methoxy-8-quinolinyl)-2-methyl-1H-imidazo[4,5-c]quinoline forpossible use as an antimalarial agent. Subsequently, syntheses ofvarious substituted 1H-imidazo[4,5-c]quinolines were reported. Forexample, Jain et al., J. Med. Chem. 11, pp. 87-92 (1968), synthesizedthe compound 1-[2-(4-piperidyl)ethyl]-1H-imidazo[4,5-c]quinoline as apossible anticonvulsant and cardiovascular agent. Also, Baranov et al.,Chem. Abs. 85, 94362 (1976), have reported several2-oxoimidazo[4,5-c]quinolines, and Berenyi et al., J. Heterocyclic Chem.18, 1537-1540 (1981), have reported certain2-oxoimidazo[4,5-c]quinolines.

Certain 1H-imidazo[4,5-c]quinolin-4-amines and 1- and 2-substitutedderivatives thereof were later found to be useful as antiviral agents,bronchodilators and immunomodulators. These are described in, interalia, U.S. Pat. Nos. 4,689,338; 4,698,348; 4,929,624; 5,037,986;5,268,376; 5,346,905; and 5,389,640, all of which are incorporatedherein by reference.

There continues to be interest in the imidazoquinoline ring system. Forexample, EP 894 797 describes imidazoquinoline compounds that bear anamide containing substituent at the 1-position. The active compounds ofthis series require a terminal amine substituent that may beincorporated into a heterocyclic ring. As another example, WO 00/09506describes imidazopyridine and imidazoquinoline compounds that may havean amide or urea containing substituent at the 1-position. The compoundsdescribed in this publication as having utility contain a 1-substituentwherein the amide or urea nitrogen is part of a heterocyclic ring.Despite these attempts to identify compounds that are useful as immuneresponse modifiers, there is a continuing need for compounds that havethe ability to modulate the immune response, by induction of cytokinebiosynthesis or other mechanisms.

SUMMARY OF THE INVENTION

We have found a new class of compounds that are useful in inducingcytokine biosynthesis in animals. Accordingly, this invention providesimidazoquinoline-4-amine and tetrahydroimidazoquinoline-4-aminecompounds that have an amide containing substituent at the 1-position.The compounds which have been found to be useful inducers of cytokinebiosynthesis are defined by Formulae (I), (Ia), and (Ib), which aredefined in more detail infra. These compounds share the generalstructural formula (I):

wherein R₁, R₂, and R are as defined herein for each class of compoundshaving formulas (I), (Ia), and (Ib). The invention also provides novelcompounds of formulas (Ic), (Id), and (Ie) as defined herein, whichcompounds are also useful as immune response modifiers and which alsohave the same general structural formula (I) above.

The compounds of Formulae (I), (Ia), (lb), (Ic), (Id), and (Ie) areuseful as immune response modifiers due to their ability to inducecytokine biosynthesis and otherwise modulate the immune response whenadministered to animals. This makes the compounds useful in thetreatment of a variety of conditionssuch as viral diseases and tumorsthat are responsive to such changes in the immune response.

The invention further provides pharmaceutical compositions containingthe immune response modifying compounds, and methods of inducingcytokine biosynthesis in an animal, treating a viral infection in ananimal, and/or treating a neoplastic disease in an animal byadministering a compound of Formula (I), (la), (lb), (Ic), (Id), or (Ie)to the animal.

In addition, methods of synthesizing the compounds of the invention andintermediates useful in the synthesis of these compounds are provided.

DETAILED DESCRIPTION OF THE INVENTION

As mentioned earlier, we have found that certain compounds inducecytokine biosynthesis and modify the immune response in animals. Suchcompounds are represented by Formulae (I), (Ia), (Ib), (Ic), (Id), and(Ie), as shown below.

The invention provides pharmaceutical compositions containing atherapeutically effective amount of a compound of Formula (I):

wherein

R₁ is -alkyl-NR₃—CO—R₄ or -alkenyl-NR₃—CO—R₄ wherein R₄ is aryl,heteroaryl, alkyl or alkenyl, each of which may be unsubstituted orsubstituted by one or more substituents selected from the groupconsisting of:

-alkyl;

-alkenyl;

-alkynyl;

-(alkyl)₀₋₁-aryl;

-(alkyl)₀₋₁-(substituted aryl);

-(alkyl)₀₋₁-heteroaryl;

-(alkyl)₀₋₁-(substituted heteroaryl);

—O-alkyl;

—O-(alkyl)₀₋₁-aryl;

—O-(alkyl)₀₋₁-(substituted aryl);

—O-(alkyl)₀₋₁-heteroaryl;

—O-(alkyl)₀₋₁-(substituted heteroaryl);

—CO-aryl;

—CO-(substituted aryl);

—CO-heteroaryl;

—CO-(substituted heteroaryl);

—COOH;

—CO—O-alkyl;

—CO-alkyl;

—S(O)₀₋₂-alkyl;

—S(O)₀₋₂-(alkyl)₀₋₁-aryl;

—S(O)₀₋₂-(alkyl)₀₋₁-(substituted aryl);

—S(O)₀₋₂-(alkyl)₀₋₁-heteroaryl;

—S(O)₀₋₂-(alkyl)₀₋₁-(substituted heteroaryl);

—P(O)(OR₃)₂;

—NR₃—CO—O-alkyl;

—N₃;

-halogen;

—NO₂;

—CN;

-haloalkyl;

—O-haloalkyl;

—CO-haloalkyl;

—OH;

—SH; and in the case of alkyl, alkenyl, or heterocyclyl, oxo;

or R₄ is

wherein R₅ is an aryl, (substituted aryl), heteroaryl, (substitutedheteroaryl), heterocyclyl or (substituted heterocyclyl) group;

R₂ is selected from the group consisting of:

-hydrogen;

-alkyl;

-alkenyl;

-aryl;

-(substituted aryl);

-heteroaryl;

-(substituted heteroaryl);

-heterocyclyl;

-(substituted heterocyclyl);

-alkyl-O-alkyl;

-alkyl-O-alkenyl; and

-alkyl or alkenyl substituted by one or more substituents selected fromthe group consisting of:

—OH;

-halogen;

—N(R₃)₂;

—CO—N(R₃)₂;

—CO—C₁₋₁₀ alkyl;

—CO—O—C₁₋₁₀ alkyl;

—N₃;

-aryl;

-(substituted aryl);

-heteroaryl;

-(substituted heteroaryl);

-heterocyclyl;

-(substituted heterocyclyl);

—CO-aryl; and

—CO-heteroaryl;

each R₃ is independently selected from the group consisting of hydrogen;C₁₋₁₀ alkyl-heteroaryl; C₁₋₁₀ alkyl-(substituted heteroaryl); C₁₋₁₀alkyl-aryl; C₁₋₁₀ alkyl-(substituted aryl) and C₁₋₁₀ alkyl;

n is 0 to 4;

and each R present is independently selected from the group consistingof C₁₋₁₀ alkyl C₁₋₁₀ alkoxy, halogen and trifluoromethyl, or apharmaceutically acceptable salt thereof, in combination with atherapeutically effective carrier.

The invention also provides pharmaceutical compositions comprising atherapeutically effective amount of a compound of Formula (Ia):

wherein

R₁ is -alkyl-NR₃—CO—R₄ or -alkenyl-NR₃—CO—R₄ wherein R₄ is aryl,heteroaryl, alkyl or alkenyl, each of which may be unsubstituted orsubstituted by one or more substituents selected from the groupconsisting of:

-heterocyclyl;

-(substituted heterocyclyl);

-(alkyl)₀₋₁heterocyclyl;

-(alkyl)₀₋₁(substituted heterocyclyl);

—O-(alkyl)₀₋₁heterocyclyl;

—O-(alkyl)₀₋₁(substituted heterocyclyl);

—S(O)₀₋₂-(alkyl)₀₋₁heterocyclyl; and

—S(O)₀₋₂-(alkyl)₀₋₁(substituted heterocyclyl);

R₂ is selected from the group consisting of:

-hydrogen;

-alkyl;

-alkenyl;

-aryl;

-(substituted aryl);

-heteroaryl;

-(substituted heteroaryl);

-heterocyclyl;

-(substituted heterocyclyl);

-alkyl-O-alkyl;

-alkyl-O-alkenyl; and

-alkyl or alkenyl substituted by one or more substituents selected fromthe group consisting of:

—OH;

-halogen;

—N(R₃)₂;

—CO—N(R₃)₂;

—CO—C₁₋₁₀ alkyl;

—CO—O—C₁₋₁₀ alkyl;

—N₃;

-aryl;

-(substituted aryl);

-heteroaryl;

-(substituted heteroaryl);

-heterocyclyl;

-(substituted heterocyclyl);

—CO-aryl; and

—CO-heteroaryl;

each R₃ is independently selected from the group consisting of hydrogen;C₁₋₁₀ alkyl-heteroaryl; C₁₋₁₀ alkyl-(substituted heteroaryl); C₁₋₁₀alkyl-aryl; C₁₋₁₀ alkyl-(substituted aryl) and C₁₋₁₀ alkyl;

n is 0to 4;

and each R present is independently selected from the group consistingof C₁₋₁₀ alkyl, C₁₋₁₀ alkoxy, halogen and trifluoromethyl, or apharmaceutically acceptable salt thereof, in combination with apharmaceutically acceptable carrier.

The invention further provides pharmaceutical compositions comprising atherapeutically effective amount of a compound of Formula (Ib):

wherein

R₁ is -alkyl-NR₃—CO—R₄ or -alkenyl-NR₃—CO—R₄ wherein R₄ is heterocyclylwhich may be unsubstituted or substituted by one or more substituentsselected from the group consisting of:

-alkyl;

-alkenyl;

-alkynyl;

-(alkyl)₀₋₁-aryl;

-(alkyl)₀₋₁-(substituted aryl);

-(alkyl)₀₋₁-heterocyclyl;

-(alkyl)₀₋₁-(substituted heterocyclyl);

-(alkyl)₀₋₁-heteroaryl;

-(alkyl)₀₋₁-(substituted heteroaryl);

—O-alkyl;

—O-(alkyl)₀₋₁-aryl;

—O-(alkyl)₀₋₁-(substituted aryl);

—O-(alkyl)₀₋₁-heterocyclyl;

—O-(alkyl)₀₋₁-(substituted heterocyclyl);

—O-(alkyl)₀₋₁-heteroaryl;

—O-(alkyl)₀₋₁-(substituted heteroaryl);

—CO-aryl;

—CO-(substituted aryl);

—CO-heteroaryl;

—CO-(substituted heteroaryl);

—COOH;

—CO—O-alkyl;

—CO-alkyl;

—S(O)₀₋₂-alkyl;

—S(O)₀₋₂-(alkyl)₀₋₁-aryl;

—S(O)₀₋₂-(alkyl)₀₋₁-(substituted aryl);

—S(O)₀₋₂-(alkyl)₀₋₁-heterocyclyl;

—S(O)₀₋₂-(alkyl)₀₋₁-(substituted heterocyclyl);

—S(O)₀₋₂-(alkyl)₀₋₁-heteroaryl;

—S(O)₀₋₂-(alkyl)₀₋₁-(substituted heteroaryl);

—P(O)(OR₃)₂;

—NR₃—CO—O-alkyl;

—N₃;

-halogen;

—NO₂;

—CN;

-haloalkyl;

—O-haloalkyl;

—CO-haloalkyl;

—OH;

—SH;

or R₄ is

wherein R₅ is an aryl, (substituted aryl), heteroaryl, (substitutedheteroaryl), heterocyclyl or (substituted heterocyclyl) group;

R₂ is selected from the group consisting of:

-hydrogen;

-alkyl;

-alkenyl;

-aryl;

-(substituted aryl);

-heteroaryl;

-(substituted heteroaryl);

-heterocyclyl;

-(substituted heterocyclyl);

-alkyl-O-alkyl;

-alkyl-O-alkenyl; and

-alkyl or alkenyl substituted by one or more substituents selected fromthe group consisting of:

—OH;

-halogen;

—N(R₃)₂;

—CO—N(R₃)₂;

—CO—C₁₋₁₀ alkyl;

—CO—O—C₁₋₁₀ alkyl;

—N₃;

-aryl;

-(substituted aryl);

-heteroaryl;

-(substituted heteroaryl);

-heterocyclyl;

-(substituted heterocyclyl);

—CO-aryl; and

—CO-heteroaryl;

each R₃ is independently selected from the group consisting of hydrogen;C₁₋₁₀ alkyl-heteroaryl; C₁₋₁₀ alkyl-(substituted heteroaryl); C₁₋₁₀alkyl-aryl; C₁₋₁₀ alkyl-(substituted aryl) and C₁₋₁₀ alkyl;

n is 0 to 4;

and each R present is independently selected from the group consistingof C₁₋₁₀ alkyl, C₁₋₁₀ alkoxy, halogen and trifluoromethyl, or apharmaceutically acceptable salt thereof, in combination with apharmaceutically acceptable carrier.

The invention also provides compounds that are useful as immune responsemodifiers. One such class of compounds has structural Formula (Ic):

wherein

R₁ is -alkyl-NR₃—CO—R₄ or -alkenyl-NR₃—CO—R₄ wherein R₄ is aryl,heteroaryl, heterocyclyl, alkyl or alkenyl, each of which may beunsubstituted or substituted by one or more substituents selected fromthe group consisting of:

-alkyl;

-alkenyl;

-alkynyl;

-(alkyl)₀₋₁-aryl;

-(alkyl)₀₋₁-(substituted aryl);

-(alkyl)₀₋₁-heteroaryl;

-(alkyl)₀₋₁-(substituted heteroaryl);

-(alkyl)₀₋₁-heterocyclyl;

-(alkyl)₀₋₁-(substituted heterocyclyl);

—O-alkyl;

—O-(alkyl)₀₋₁-aryl;

—O-(alkyl)₀₋₁-(substituted aryl);

—O-(alkyl)₀₋₁-heteroaryl;

—O-(alkyl)₀₋₁-(substituted heteroaryl);

—O-(alkyl)₀₋₁-heterocyclyl;

—O-(alkyl)₀₋₁-(substituted heterocyclyl);

—CO-aryl;

—CO-(substituted aryl);

—CO-heteroaryl;

—CO-(substituted heteroaryl);

—COOH;

—CO—O-alkyl;

—CO-alkyl;

—S(O)₀₋₂-alkyl;

—S(O)₀₋₂-(alkyl)₀₋₁-aryl;

—S(O)₀₋₂-(alkyl)₀₋₁-(substituted aryl);

—S(O)₀₋₂-(alkyl)₀₋₁-heteroaryl;

—S(O)₀₋₂-(alkyl)₀₋₁-(substituted heteroaryl);

—S(O)₀₋₂-(alkyl)₀₋₁-heterocyclyl;

—S(O)₀₋₂-(alkyl)₀₋₁-(substituted heterocyclyl);

—P(O)(OR₃)₂;

—NR₆—CO—O-alkyl;

—N₃;

-halogen;

—NO₂;

—CN;

-haloalkyl;

—O-haloalkyl;

—CO-haloalkyl;

—OH;

—SH; and in the case of alkyl, alkenyl, or heterocyclyl, oxo;

or R₄ is

wherein R₅ is an aryl, (substituted aryl), heteroaryl, (substitutedheteroaryl), heterocyclyl or (substituted heterocyclyl) group;

R₂ is selected from the group consisting of:

-hydrogen;

-alkyl;

-alkenyl;

-aryl;

-(substituted aryl);

-heteroaryl;

-(substituted heteroaryl);

-heterocyclyl;

-(substituted heterocyclyl);

-alkyl-O-alkyl;

-alkyl-O-alkenyl; and

-alkyl or alkenyl substituted by one or more substituents selected fromthe group consisting of:

—OH;

-halogen;

—N(R₆)₂;

—CO—N(R₆)₂;

—CO—C₁₋₁₀ alkyl;

—CO—O—C₁₋₁₀ alkyl;

—N₃;

-aryl;

-(substituted aryl);

-heteroaryl;

-(substituted heteroaryl);

-heterocyclyl;

-(substituted heterocyclyl);

—CO-aryl; and

—CO-heteroaryl;

R₃ is selected from the group consisting of C₁₋₁₀ alkyl-heteroaryl;C₁₋₁₀ alkyl-(substituted heteroaryl); C₁₋₁₀ alkyl-aryl; C₁₋₁₀alkyl-(substituted aryl) and C₁₋₁₀ alkyl;

each R₆ is independently selected from the group consisting of hydrogen;C₁₋₁₀ alkyl-heteroaryl; C₁₋₁₀ alkyl-(substituted heteroaryl); C₁₋₁₀alkyl-aryl; C₁₋₁₀ alkyl-(substituted aryl) and C₁₋₁₀ alkyl;

n is 0 to 4;

and each R present is independently selected from the group consistingof C₁₋₁₀ alkyl, C₁₋₁₀ alkoxy, halogen and trifluoromethyl, or apharmaceutically acceptable salt thereof.

Another class of compounds provided by the invention is described byFormula (Id):

wherein

R₁ is -alkyl-NR₃—CO—R₄ or -alkenyl-NR₃—CO—R₄ wherein R₄ is aryl orheteroaryl which may be unsubstituted or substituted by one or moresubstituents selected from the group consisting of:

-alkyl;

-alkenyl;

-alkynyl;

-(alkyl)₀₋₁-aryl;

-(alkyl)₀₋₁-(substituted aryl);

-(alkyl)₀₋₁-heteroaryl;

-(alkyl)₀₋₁-(substituted heteroaryl);

-(alkyl)₀₋₁-heterocyclyl;

-(alkyl)₀₋₁-(substituted heterocyclyl);

—O-alkyl;

—O-(alkyl)₀₋₁-aryl;

—O-(alkyl)₀₋₁-(substituted aryl);

—O-(alkyl)₀₋₁-heteroaryl;

—O-(alkyl)₀₋₁-(substituted heteroaryl);

—O-(alkyl)₀₋₁-heterocyclyl;

—O-(alkyl)₀₋₁-(substituted heterocyclyl);

—CO-aryl;

—CO-(substituted aryl);

—CO-heteroaryl;

—CO-(substituted heteroaryl);

—COOH;

—CO—O-alkyl;

—CO-alkyl;

—S(O)₀₋₂-alkyl;

—S(O)₀₋₂-(alkyl)₀₋₁-aryl;

—S(O)₀₋₂-(alkyl)₀₋₁-(substituted aryl);

—S(O)₀₋₂-(alkyl)₀₋₁-heteroaryl;

—S(O)₀₋₂-(alkyl)₀₋₁-(substituted heteroaryl);

—S(O)₀₋₂-(alkyl)₀₋₁-heterocyclyl;

—S(O)₀₋₂-(alkyl)₀₋₁-(substituted heterocyclyl);

—P(O)(OR₃)₂;

—NR₃—CO—O-alkyl;

—N₃;

-halogen;

—NO₂;

—CN;

-haloalkyl;

—O-haloalkyl;

—CO-haloalkyl;

—OH; and

—SH;

R₂ is selected from the group consisting of:

-hydrogen;

-alkyl;

-alkenyl;

-aryl;

-(substituted aryl);

-heteroaryl;

-(substituted heteroaryl);

-heterocyclyl;

-(substituted heterocyclyl);

-alkyl-O-alkyl;

-alkyl-O-alkenyl; and

-alkyl or alkenyl substituted by one or more substituents selected fromthe group consisting of:

—OH;

-halogen;

—N(R₃)₂;

—CO—N(R₃)₂;

—CO—C₁₋₁₀ alkyl;

—CO—C₁₋₁₀ alkyl;

—N₃;

-aryl;

-(substituted aryl);

-heteroaryl;

-(substituted heteroaryl);

-heterocyclyl;

-(substituted heterocyclyl);

—CO-aryl; and

—CO-heteroaryl;

each R₃ is independently selected from the group consisting of hydrogen;C₁₋₁₀ alkyl-heteroaryl; C₁₋₁₀ alkyl-(substituted heteroaryl); C₁₋₁₀alkyl-aryl; C₁₋₁₀ alkyl-(substituted aryl) and C₁₋₁₀ alkyl;

n is 0to 4;

and each R present is independently selected from the group consistingof C₁₋₁₀ alkyl, C₁₋₁₀ alkoxy, halogen and trifluoromethyl, or apharmaceutically acceptable salt thereof,

with the proviso that R₄ is not an unsubstituted benzene ring, and thatwhen R₄ is a substituted benzene ring the substituents are selected fromthe group consisting of C₁₋₂₀ alkyl, C₂₋₂₀ alkoxy, C₁₋₂₀ alkylthio,hydroxy, haloalkyl, haloalkylcarbonyl, haloalkoxy, C₁₋₂₀alkylcarbonyl,C₁₋₂₀alkenylcarbonyl, arylcarbonyl, heteroarylcarbonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocycloalkyl, nitrile,C₁₋₂₀ alkoxycarbonyl, C₁₋₂₀alkanoyloxy, C₁₋₂₀alkanoylthio, oxo and—(C₁₋₁₀alkyl)-NR₃—(C₁₋₁₀alkyl)-R₅,

wherein R₅ is an aryl, (substituted aryl), heteroaryl, (substitutedheteroaryl), heterocyclyl or (substituted heterocyclyl) group.

A further class of compounds provided by the invention is described byFormula (Ie):

wherein

R₁ is -alkyl-NR₃—CO—R₄ or -alkenyl-NR₃—CO—R₄ wherein R₄ is an alkyl oralkenyl group that is substituted by one or more substituents selectedfrom the group consisting of:

-alkynyl;

-(substituted aryl) wherein the substituent(s) are independentlyselected from the group consisting of alkyl, alkoxy, alkylthio, hydroxy,haloalkyl, haloalkylcarbonyl, haloalkoxy, alkylcarbonyl,alkenylcarbonyl, arylcarbonyl, heteroarylcarbonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocycloalkyl, nitrile,alkoxycarbonyl, alkanoyloxy, and alkanoylthio;

-(substituted aryl);

-heteroaryl;

-(substituted heteroaryl);

—O-alkyl;

—O-(alkyl)₀₋₁-(substituted aryl) wherein the substituent(s) areindependently selected from the group consisting of alkyl, alkoxy,alkylthio, hydroxy, haloalkyl, haloalkylcarbonyl, haloalkoxy,alkylcarbonyl, alkenylcarbonyl, arylcarbonyl, heteroarylcarbonyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocycloalkyl,nitrile, alkoxycarbonyl, alkanoyloxy, and alkanoylthio;

—O-(alkyl)₀₋₁-heteroaryl;

—O-(alkyl)₀₋₁-(substituted heteroaryl);

—CO-aryl;

—CO-(substituted aryl);

—CO-heteroaryl;

—CO-(substituted heteroaryl);

—COOH;

—CO—O-alkyl;

—CO-alkyl;

—S(O)₀₋₂-alkyl;

—S(O)₀₋₂-(alkyl)₀₋₁-aryl;

—S(O)₀₋₂-(alkyl)₀₋₁-(substituted aryl);

—S(O)₀₋₂-(alkyl)₀₋₁-heteroaryl;

—S(O)₀₋₂-(alkyl)₀₋₁-(substituted heteroaryl);

—P(O)(OR₃)₂;

—NR₃—CO—O-alkyl;

—N₃;

—NO₂;

—CN;

—O-haloalkyl;

—CO-haloalkyl;

—OH;

—SH; and oxo;

R₂ is selected from the group consisting of:

-hydrogen;

-alkyl;

-alkenyl;

-aryl;

-(substituted aryl);

-heteroaryl;

-(substituted heteroaryl);

-heterocyclyl;

-(substituted heterocyclyl);

-alkyl-O-alkyl;

-alkyl-O-alkenyl; and

-alkyl or alkenyl substituted by one or more substituents selected fromthe group consisting of:

—OH;

-halogen;

—N(R₃)₂;

—CO—N(R₃)₂;

—CO—C₁₋₁₀ alkyl;

—CO—O—C₁₋₁₀ alkyl;

—N₃;

-aryl;

-(substituted aryl);

-heteroaryl;

-(substituted heteroaryl);

-heterocyclyl;

-(substituted heterocyclyl);

—CO-aryl; and

—CO-heteroaryl;

each R₃ is independently selected from the group consisting of hydrogen;C₁₋₁₀ alkyl-heteroaryl; C₁₋₁₀ alkyl-(substituted heteroaryl); C₁₋₁₀alkyl-aryl; C₁₋₁₀ alkyl-(substituted aryl) and C₁₋₁₀ alkyl;

n is 0 to 4;

and each

R present is independently selected from the group consisting of C₁₋₁₀alkyl, C₁₋₁₀ alkoxy, halogen and trifluoromethyl, or a pharmaceuticallyacceptable salt thereof.

Preparation of the Compounds

Imidazoquinolines of the invention can be prepared according to ReactionScheme I where R, R₁, R₂ and n are as defined above.

In step (1) of Reaction Scheme I a 4-chloro-3-nitroquinoline of FormulaII is reacted with an amine of Formula R₁NH₂ to provide a3-nitroquinolin-4-amine of Formula III. The reaction can be carried outby adding amine to a solution of a compound of Formula II in a suitablesolvent such as chloroform or dichloromethane and optionally heating.Many quinolines of Formula II are known compounds (see for example, U.S.Pat. No. 4,689,338 and references cited therein).

In step (2) of Reaction Scheme I a 3-nitroquinolin-4-amine of FormulaIII is reduced to provide a quinoline-3,4-diamine of Formula IV.Preferably, the reduction is carried out using a conventionalheterogeneous hydrogenation catalyst such as platinum on carbon orpalladium on carbon. The reaction can conveniently be carried out on aParr apparatus in a suitable solvent such as isopropyl alcohol ortoluene.

In step (3) of Reaction Scheme I a quinoline-3,4-diamine of Formula IVis reacted with a carboxylic acid or an equivalent thereof to provide a1H-imidazo[4,5-c]quinoline of Formula V. Suitable equivalents tocarboxylic acid include acid halides, orthoesters, and 1,1-dialkoxyalkylalkanoates. The carboxylic acid or equivalent is selected such that itwill provide the desired R₂ substituent in a compound of Formula V. Forexample, triethyl orthoformate will provide a compound where R₂ ishydrogen and triethyl orthoacetate will provide a compound where R₂ ismethyl. The reaction can be run in the absence of solvent or in an inertsolvent such as toluene. The reaction is run with sufficient heating todrive off any alcohol or water formed as a byproduct of the reaction.

In step (4) of Reaction Scheme I a 1H-imidazo[4,5-c]quinoline of FormulaV is oxidized to provide a 1H-imidazo[4,5-c]quinoline-5N-oxide ofFormula VI using a conventional oxidizing agent that is capable offorming N-oxides. Preferred reaction conditions involve reacting asolution of a compound of Formula V in chloroform with3-chloroperoxybenzoic acid at ambient conditions.

In step (5) of Reaction Scheme I a 1H-imidazo[4,5-c]quinoline-5N-oxideof Formula VI is aminated to provide a 1H-imidazo[4,5-c]quinolin-4-amineof Formula VII which is a subgenus of Formula I. Step (5) involves (i)reacting a compound of Formula VI with an acylating agent and then (ii)reacting the product with an aminating agent. Part (i) of step (5)involves reacting an N-oxide of Formula VI with an acylating agent.Suitable acylating agents include alkyl- or arylsulfonyl chlorides(e.g., benezenesulfonyl chloride, methanesulfonyl chloride,p-toluenesulfonyl chloride). Arylsulfonyl chlorides are preferred.Para-toluenesulfonyl chloride is most preferred. Part (ii) of step (5)involves reacting the product of part (i) with an excess of an aminatingagent. Suitable aminating agents include ammonia (e.g., in the form ofammonium hydroxide) and ammonium salts (e.g., ammonium carbonate,ammonium bicarbonate, ammonium phosphate). Ammonium hydroxide ispreferred. The reaction is preferably carried out by dissolving theN-oxide of Formula VI in an inert solvent such as dichloromethane,adding the aminating agent to the solution, and then slowly adding theacylating agent. The product or a pharmaceutically acceptable saltthereof can be isolated using conventional methods.

Alternatively, step (5) may be carried out by (i) reacting an N-oxide ofFormula VI with an isocyanate and then (ii) hydrolyzing the resultingproduct. Part (i) involves reacting the N-oxide with an isocyanatewherein the isocyanato group is bonded to a carbonyl group. Preferredisocyanates include trichloroacetyl isocyanante and aroyl isocyanatessuch as benzoyl isocyanate. The reaction of the isocyanate with theN-oxide is carried out under substantially anhydrous conditions byadding the isocyanate to a solution of the N-oxide in an inert solventsuch as chloroform or dichloromethane. Part (ii) involves hydrolysis ofthe product from part (i). The hydrolysis can be carried out byconventional methods such as heating in the presence of water or a loweralkanol optionally in the presence of a catalyst such as an alkali metalhydroxide or lower alkoxide.

Compounds of the invention can also be prepared according to ReactionScheme II where R, R₂, R₄ and n are as defined above and m is 1-20.

In Reaction Scheme II an aminoalkyl substituted1H-imidazo[4,5-c]quinolin-4-amine of Formula VIII is reacted with anacid chloride of Formula IX to provide a compound of Formula X which isa subgenus of Formula I. The reaction can be carried out by adding asolution of the acid chloride in a suitable solvent such as pyridine ordichloromethane to a solution of a compound of Formula VIII either atambient temperature or at a reduced temperature. Many1H-imidazo[4,5-c]quinolin-4-amines of Formula VIII are known compounds,see for example U.S. Pat. No. 6,069,149 (Nanba), the disclosure of whichis incorporated by reference herein; others can be readily preparedusing known synthetic methods. Many acid chlorides of Formula IX arecommercially available; others can be readily prepared using knownsynthetic methods. The product or a pharmaceutically acceptable saltthereof can be isolated using conventional methods.

Compounds of the invention can also be prepared according to ReactionScheme III where R, R₂, R₄ and n are as defined above and m is 1-20.

In Reaction Scheme III an aminoalkyl substituted1H-imidazo[4,5-c]quinolin-4-amine of Formula VIII is reacted with anacid of Formula XI to provide a compound of Formula X which is asubgenus of Formula I. The reaction can be run at ambient temperature ina solvent such as dichloromethane or pyridine using a standard couplingreagent such as 1,3-dicyclohexylcarbodiimide or1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide. The product or apharmaceutically acceptable salt thereof can be isolated usingconventional methods.

Compounds of the invention can also be prepared according to ReactionScheme IV where R, R₂, R₄ and n are as defined above and m is 1-20.

In Reaction Scheme IV an aminoalkyl substituted1H-imidazo[4,5-c]quinolin-4-amine of Formula VIII is reacted with anacid anhydride of Formula XII provide a compound of Formula X which is asubgenus of Formula I. The reaction can be run at ambient temperature inan inert solvent such as dichloromethane in the presence of a base suchas N,N-diisopropylethylamine or pyridine. Many acid anhydrides ofFormula XII are commercially available; others may be readily preparedusing known synthetic methods. The product or a pharmaceuticallyacceptable salt thereof can be isolated using conventional methods.

Tertiary amides of the invention can be prepared according to ReactionScheme V where R, R₂, R₃, R₄ and n are as defined above except that R₃is other than hydrogen and m is 1-20.

In step (1) of Reaction Scheme V an aminoalkyl substituted1H-imidazo[4,5-c]quinolin-4-amine of Formula VIII is reacted with analdehyde of Formula XIII to provide a secondary amine of Formula XIV.Preferably, the reductive amination is carried out using sodiumtriacetoxyborohydride. The reaction can be carried out by adding thesodium triacetoxyborohydride to a solution of the amine and the aldehydein an inert solvent such as dichloromethane. The secondary amine or asalt thereof can be isolated using conventional methods.

In step (2) of Reaction Scheme V the secondary amine of Formula XIV isacylated to provide a compound of Formula XV which is a subgenus ofFormula I. The reaction can be carried out by reacting the secondaryamine of Formula XIV with an acid, acid chloride or an acid anhydrideaccording to the methods of Reaction Schemes III, II and IV above. Theproduct or a pharmaceutically acceptable salt thereof can be isolatedusing conventional methods.

Tetrahydroimidazoquinolines of the invention can be prepared accordingto Reaction Scheme VI where R₂, R₃ and R₄ are as defined above and m is1-20.

In step (1) of Reaction Scheme VI an aminoalkyl substituted1H-imidazo[4,5-c]quinolin-4-amine of Formula XVI is reduced to providean aminoalkyl substituted6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-4-amine of Formula XVII.Preferably the reduction is carried out by suspending or dissolving thecompound of Formula XVI in trifluoroacetic acid, adding a catalyticamount of platinum (IV) oxide, and then subjecting the mixture tohydrogen pressure. The reaction can conveniently be carried out on aParr apparatus. The product or a salt thereof can be isolated usingconventional methods.

In step (2) of Reaction Scheme VI an aminoalkyl substituted6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-4-amine of Formula XVII isreacted to provide a compound of Formula XVIII which is a subgenus ofFormula I. When R₃ is hydrogen, the reaction can be carried outaccording to the methods described in Reaction Schemes II, III and IVabove using a tetrahydroimidazoquinoline of Formula XVII in place of theimidazoquinoline of Formula VIII. When R₃ is other than hydrogen, thenthe reaction can be carried out using the method described in ReactionScheme V. The product or a pharmaceutically acceptable salt thereof canbe isolated using conventional methods.

Tetrahydroimidazoquinolines of the invention can also be preparedaccording to Reaction Scheme VII where R, R₂, R₃, R₄ and n are asdefined above and m is 1-20.

In step (1) of Reaction Scheme VII a6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolinyl tert-butylcarbamate ofFormula XIX is hydrolyzed to provide an aminoalkyl substituted6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-4-amine of Formula XX. Thereaction can be carried out dissolving the compound of Formula XIX in amixture of trifluoroacetic acid and acetonitrile and stirring at ambienttemperature. Alternatively, the compound of Formula XIX can be combinedwith dilute hydrochloric acid and heated on a steam bath.Tetrahydro-1H-imidazo[4,5-c]quinolinyl tert-butylcarbamates of FormulaXIX can be prepared using the synthetic route disclosed in U.S. Pat. No.5,352,784 (Nikolaides). The product or a salt thereof can be isolatedusing conventional methods.

In step (2) of Reaction Scheme VII an aminoalkyl substituted6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-4-amine of Formula XX isreacted to provide a compound of Formula XXI which is a subgenus ofFormula I. When R₃ is hydrogen, the reaction can be carried outaccording to the methods described in Reaction Schemes II, III and IVabove using a tetrahydroimidazoquinoline of Formula XX in place of theimidazoquinoline of Formula VIII. When R₃ is other than hydrogen, thenthe reaction can be carried out using the method described in ReactionScheme V. The product or a pharmaceutically acceptable salt thereof canbe isolated using conventional methods.

Some compounds of Formula I can be readily prepared from other compoundsof Formula I. For example, compounds wherein the R₄ substituent containsa chloroalkyl group can be reacted with an amine to provide an R₄substituent substituted by a secondary or teriary amino group; compoundswherein the R₄ substituent contains a nitro group can be reduced toprovide a compound wherein the R₄ substituent contains a primary amine.

As used herein, the terms “alkyl”, “alkenyl”, “alkynyl” and the prefix“-alk” are inclusive of both straight chain and branched chain groupsand of cyclic groups, i.e. cycloalkyl and cycloalkenyl. Unless otherwisespecified, these groups contain from 1 to 20 carbon atoms, with alkenyland alkynyl groups containing from 2 to 20 carbon atoms. Preferredgroups have a total of up to 10 carbon atoms. Cyclic groups can bemonocyclic or polycyclic and preferably have from 3 to 10 ring carbonatoms. Exemplary cyclic groups include cyclopropyl, cyclopentyl,cyclohexyl and adamantyl.

The term “haloalkyl” is inclusive of groups that are substituted by oneor more halogen atoms, including groups wherein all of the availablehydrogen atoms are replaced by halogen atoms. This is also true ofgroups that include the prefix “haloalk-”. Examples of suitablehaloalkyl groups are chloromethyl, trifluoromethyl, and the like.

The term “aryl” as used herein includes carbocyclic aromatic rings orring systems. Examples of aryl groups include phenyl, naphthyl,biphenyl, fluorenyl and indenyl. The term “heteroaryl” includes aromaticrings or ring systems that contain at least one ring hetero atom (e.g.,O, S, N). Suitable heteroaryl groups include furyl, thienyl, pyridyl,quinolinyl, isoquinolinyl, indolyl, isoindolyl, pyrrolyl, tetrazolyl,imidazo, pyrazolo, oxazolo, thiazolo and so on.

“Heterocyclyl” includes non-aromatic rings or ring systems that containat least one ring hetero atom (e.g., O, S, N). Exemplary heterocyclicgroups include pyrrolidinyl, tetrahydrofuranyl, morpholinyl,thiomorpholinyl, piperidinyl, piperazinyl, thiazolidinyl, andimidazolidinyl.

Unless otherwise specified, the terms “substituted aryl”, “substitutedheteroaryl” and “substituted heterocyclyl” indicate that the rings orring systems in question are further substituted by one or moresubstituents independently selected from the group consisting of alkyl,alkoxy, alkylthio, hydroxy, halogen, haloalkyl, haloalkylcarbonyl,haloalkoxy (e.g., trifluoromethoxy), nitro, alkylcarbonyl,alkenylcarbonyl, arylcarbonyl, heteroarylcarbonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocycloalkyl, nitrile,alkoxycarbonyl, alkanoyloxy, alkanoylthio, and, in the case ofheterocyclyl, oxo.

In structural formulas representing compounds of the invention certainbonds are represented by dashed lines. These lines mean that the bondsrepresented by the dashed line can be present or absent. Accordingly,the compounds of the invention can be either imidazoquinoline compoundsor tetrahydroimidazoquinoline compounds.

The invention is inclusive of the compounds described herein in any oftheir pharmaceutically acceptable forms, including isomers such asdiastereomers and enantiomers, salts, solvates, polymorphs, and thelike.

Pharmaceutical Compositions and Biological Activity

Pharmaceutical compositions of the invention contain a therapeuticallyeffective amount of a compound of the invention as described supra incombination with a pharmaceutically acceptable carrier.

The term “a therapeutically effective amount” means an amount of thecompound sufficient to induce a therapeutic effect, such as cytokineinduction, antitumor activity and/or antiviral activity. Although theexact amount of active compound used in a pharmaceutical composition ofthe invention will vary according to factors known to those of skill inthe art, such as the physical and chemical nature of the compound aswell as the nature of the carrier and the intended dosing regimen, it isanticipated that the compositions of the invention will containsufficient active ingredient to provide a dose of about 100 ng/kg toabout 50 mg/kg, preferably about 10 μg/kg to about 5 mg/kg, of thecompound to the subject. Any of the conventional dosage forms may beused, such as tablets, lozenges, parenteral formulations, syrups,creams, ointments, aerosol formulations, transdermal patches,transmucosal patches and the like.

The compounds of the invention can be administered as the singletherapeutic agent in the treatment regimen, or the compounds of theinvention may be administered in combination with one another or withother active agents, including additional immune response modifiers,antivirals, antibiotics, etc.

The compounds of the invention have been shown to induce the productionof certain cytokines in experiments performed according to the tests setforth below. These results indicate that the compounds are useful asimmune response modifiers that can modulate the immune response in anumber of different ways, rendering them useful in the treatment of avariety of disorders.

Cytokines whose production may be induced by the administration ofcompounds according to the invention generally include interferon-α(IFN-α) and/or tumor necrosis factor-α (TNF-α) as well as certaininterleukins (IL). Cytokines whose biosynthesis may be induced bycompounds of the invention include IFN-α, TNF-α, IL-1, 6, 10 and 12, anda variety of other cytokines. Among other effects, cytokines inhibitvirus production and tumor cell growth, making the compounds useful inthe treatment of viral diseases and tumors.

In addition to the ability to induce the production of cytokines, thecompounds of the invention affect other aspects of the innate immuneresponse. For example, natural killer cell activity may be stimulated,an effect that may be due to cytokine induction. The compounds may alsoactivate macrophages, which in turn stimulates secretion of nitric oxideand the production of additional cytokines. Further, the compounds maycause proliferation and differentiation of B-lymphocytes.

Compounds of the invention also have an effect on the acquired immuneresponse. For example, although there is not believed to be any directeffect on T cells or direct induction of T cell cytokines, theproduction of the T helper type 1 (Th1) cytokine IFN-γ is inducedindirectly and the production of the T helper type 2 cytokines IL-4,IL-5 and IL-13 are inhibited upon administration of the compounds. Thisactivity means that the compounds are useful in the treatment ofdiseases where upregulation of the Th1 response and/or downregulation ofthe Th2 response is desired. In view of the ability of compounds of theinvention to inhibit the Th2 immune response, the compounds are expectedto be useful in the treatment of atopic diseases, e.g., atopicdermatitis, asthma, allergy, allergic rhinitis; systemic lupuserythematosis; as a vaccine adjuvant for cell mediated immunity; andpossibly as a treatment for recurrent fungal diseases and chlamydia.

The immune response modifying effects of the compounds make them usefulin the treatment of a wide variety of conditions. Because of theirability to induce the production of cytokines such as IFN-α and/orTNF-α, the compounds are particularly useful in the treatment of viraldiseases and tumors. This immunomodulating activity suggests thatcompounds of the invention are useful in treating diseases such as, butnot limited to, viral diseases including genital warts; common warts;plantar warts; Hepatitis B; Hepatitis C; Herpes Simplex Virus Type I andType II; molluscum contagiosum; HIV; CMV; VZV; intraepithelialneoplasias such as cervical intraepithelial neoplasia; humanpapillomavirus (HPV) and associated neoplasias; fungal diseases, e.g.candida, aspergillus, and cryptococcal meningitis; neoplastic diseases,e.g., basal cell carcinoma, hairy cell leukemia, Kaposi's sarcoma, renalcell carcinoma, squamous cell carcinoma, myelogenous leukemia, multiplemyeloma, melanoma, non-Hodgkin's lymphoma, cutaneous T-cell lymphoma,and other cancers; parasitic diseases, e.g. pneumocystis carnii,cryptosporidiosis, histoplasmosis, toxoplasmosis, trypanosome infection,and leishmaniasis; and bacterial infections, e.g., tuberculosis, andmycobacterium avium. Additional diseases or conditions that can betreated using the compounds of the invention include eczema;eosinophilia; essential thrombocythaemia; leprosy; multiple sclerosis;Ommen's syndrome; discoid lupus; Bowen's disease; Bowenoid papulosis;and to enhance or stimulate the healing of wounds, including chronicwounds. Accordingly, the invention provides a method of inducingcytokine biosynthesis in an animal comprising administering an effectiveamount of a compound or composition of the invention to the animal.

An amount of a compound effective to induce cytokine biosynthesis is anamount sufficient to cause one or more cell types, such as monocytes,macrophages, dendritic cells and B-cells to produce an amount of one ormore cytokines such as, for example, IFN-α, TNF-α, IL-1,6,10 and 12 thatis increased over the background level of such cytokines. The preciseamount will vary according to factors known in the art but is expectedto be a dose of about 100 ng/kg to about 50 mg/kg, preferably about 10μg/kg to about 5 mg/kg. The invention also provides a method of treatinga viral infection in an animal and a method of treating a neoplasticdisease in an animal comprising administering an effective amount of acompound or composition of the invention to the animal. An amounteffective to treat or inhibit a viral infection is an amount that willcause a reduction in one or more of the manifestations of viralinfection, such as viral lesions, viral load, rate of virus production,and mortality as compared to untreated control animals. The preciseamount will vary according to factors known in the art but is expectedto be a dose of about 100 ng/kg to about 50 mg/kg, preferably about 10μg/kg to about 5 mg/kg. An amount of a compound effective to treat aneoplastic condition is an amount that will cause a reduction in tumorsize or in the number of tumor foci. Again, the precise amount will varyaccording to factors known in the art but is expected to be a dose ofabout 100 ng/kg to about 50 mg/kg, preferably about 10 μg/kg to about 5mg/kg.

The invention is further described by the following examples, which areprovided for illustration only and are not intended to be limiting inany way.

EXAMPLE 1 N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamide

A suspension of 1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (2.0g, 7.8 mmol) in pyridine (1 L) was warmed to 60° C. to dissolve thestarting material. The solution was cooled to about 30° C. and thenbenzoyl chloride (1.1 g, 7.8 mmol) diluted with pyridine (100 mL) wasslowly added. After 1 hour analysis by high performance liquidchromatography (HPLC) indicated that some starting material remained.Additional benzoyl chloride (0.3 g) was added and the reaction waswarmed to 50° C. overnight. The reaction mixture was concentrated undervacuum. The resulting residue was combined with chloroform (200 mL) and1% sodium carbonate (200 mL). The organic layer was separated and thenconcentrated under vacuum. The resulting residue was combined withpropyl acetate (30 mL) and heated on a steam bath to dissolve theresidue. The solution was allowed to cool. The resulting precipitate wasisolated by filtration to provideN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamide as asolid, m.p. 210-212° C. Analysis: Calculated for C₂₁H₂₁N₅O: %C, 70.18;%H, 5.89: %N, 19.48; Found: %C, 69.49; %H, 5.97; %N, 19.64. ¹H NMR (500MHz, DMSO-d₆) δ8.48 (t, J=6.0 Hz, 1H), 8.22 (s, 1H), 8.04 (d, J=8.0 Hz,1H), 7.78 (d, J=8.0 Hz, 2H), 7.61 (d, J=8.0 Hz, 1H), 7.50 (t, J=8.0 Hz,1H), 7.43 (m, 3H), 7.21 (t, J=8.0 Hz, 1H), 6.62 (broad s, 2H), 4.64 (t,J=7.0 Hz, 2H), 3.30 (q, J=6.0 Hz, 2H), 1.92 (quintet, J=7.0 Hz, 2H),1.58 (quintet, J=7.0 Hz, 2H); MS (EI) m/e 359.1746 (359.1746 calcd forC₂₁H₂₁N₅O).

EXAMPLE 2 N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamideHydrochloride Hydrate

N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamide (1 g) wasdissolved in isopropanol. Hydrochloric acid (1 eq of 12N) was added. Theresulting precipitate was isolated by filtration to provide 1 g ofN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamidehydrochloride hydrate as a solid, m.p. 254-256° C. Analysis: Calculatedfor C₂₁H₂₁N₅O.HCl.1.5 H₂O: %C, 59.63; %H, 5.96; %N, 16.56; Found: %C59.61; %H, 6.04; %N, 16.64. ¹H NMR (500 MHz, DMSO-d₆) δ13.80 (broad s,1H), 9.15 (broad s, 2H), 8.56 (s, 1H), 8.50 (t, J=6.0 Hz, 1H), 8.23 (d,J=8.0 Hz, 1H), 7.83 (d, J=8.0 Hz, 1H), 7.76 (d, J=8.0 Hz, 2H), 7.71 (t,J=8.0 Hz, 1H), 7.53 (t, J=8.0 Hz, 1H), 7.50 (t, J=8.0 Hz, 1H), 7.42 (t,J=8.0 Hz, 2H), 4.72 (t, J=7.0 Hz, 2H), 3.30 (q, J=7.0 Hz, 2H), 1.93(quintet, J=7.0 Hz, 2H), 1.61 (quintet, J=7.0 Hz, 2H).

EXAMPLE 3N¹-[4-(4-Amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamide

Using the general method of Example 1,1-(4-aminobutyl)-2-propyl-1H-imidazo[4,5-c]quinolin-4-amine (0.55 g, 1.8mmol) was reacted with benzoyl chloride (0.26 g, 1.8 mmol) to provideN¹-[4-(4-amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamideas a solid, m.p. 173-174° C. ¹H NMR (500 MHz, DMSO-d₆) δ8.80 (broad s,2H), 8.46 (t, J=6.0 Hz, 1H), 8.20 (d, J=8.0 Hz, 1H), 7.81 (d, J=8.4 Hz,1H), 7.76 (d, J=7.4 Hz, 2H), 7.67 (t, J=7.4 Hz, 1H), 7.49 (m, 2H), 7.43(t, J=7.5 Hz, 2H), 4.63 (t, J=7.0 Hz, 2H), 3.34 (m, 2H), 2.97 (t, J=7.0Hz, 2H), 1.85 (m, 4H), 1.72 (quintet, J=7.0 Hz, 2H), 1.01 (t, J=7.0 Hz,3H); MS (EI) m/e 401.2210 (401.2216 calcd for C₂₄H₂₇N₅O)

EXAMPLE 4N¹-[4-(4-Amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamide

Using the general method of Example 1,1-(4-aminobutyl)-2-methyl-1H-imidazo[4,5-c]quinolin-4-amine (0.5 g, 1.8mmol) was reacted with benzoyl chloride (0.26 g, 1.8mmol) to provideN¹-[4-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamideas a solid, m.p. 164-170° C. ¹H NMR (500 MHz, DMSO-d₆) δ8.47 (t, J=6.0Hz, 1H), 8.01 (d, J=8.0 Hz, 1H), 7.78 (d, J=8.0 Hz, 2H), 7.59 (dd,J=8.0, 1.2 Hz, 1H), 7.50 (t, J=8.0 Hz, 1H), 7.43 (t, J=8.0 Hz, 2H), 7.38(dt, J=8.0, 1.2 Hz, 1H), 7.17 (dt, J=8.0, 1.2 Hz, 1H), 6.48 (broad s,2H), 4.53 (t, J=7.0 Hz, 2H), 3.31 (q, J=6.0 Hz, 2H), 2.60 (s, 3H), 1.88(quintet, J=7.0 Hz, 2H), 1.68 (quintet, J=7.0 Hz, 2H); MS (EI) m/e373.1903 (373.1903 calcd for C₂₂H₂₃N₅O)

EXAMPLE 5N¹-[4-(4-Amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamide

Using the general method of Example 1,1-(4-aminobutyl)-2-ethyl-1H-imidazo[4,5-c]quinolin-4-amine (0.5 g, 1.76mmol) was reacted with benzoyl chloride (0.25 g, 1.76 mmol) to provideN¹-[4-(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamide asa solid, m.p. 203-206° C. ¹H NMR (500 MHz, DMSO-d₆) δ8.48 (t, J=6.0 Hz,1H), 8.00 (d, J=8.0 Hz, 1H), 7.79 (d, J=8.0 Hz, 2H), 7.60 (dd, J=8.0,1.0 Hz, 1H), 7.50 (t, J=8.0 Hz, 1H), 7.43 (t, J=8.0 Hz, 2H), 7.38 (t,J=8.0 Hz, 1H), 7.17 (t, J=8.0 Hz, 1H), 6.47 (broad s, 2H), 4.53 (t,J=7.0 Hz, 2H), 3.32 (q, J=6.0 Hz, 2H), 2.95 (q, J=7.0 Hz, 2H), 1.87(quintet, J=7.0 Hz, 2H), 1.70 (quintet, J=7.0 Hz, 2H), 1.35 (t, J=7.0Hz, 3H); MS (EI) m/e 387.2058 (387.2059 calcd for C₂₃H₂₅N₅O).

EXAMPLE 6N¹-[4-(4-Amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamide

1-(4-Aminobutyl)-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine (0.5 g, 1.6mmol) was combined with pyridine (50 mL) and heated to 50° C. Benzoylchloride (0.22 g, 1.6 mmol) was added via a pipette. After 1 houranalysis by HPLC indicated that all of the starting material was goneand that several products had formed. The reaction mixture wasconcentrated under vacuum. The residue was combined with dichloromethaneand aqueous sodium bicarbonate. The organic layer was separated and thenconcentrated under vacuum. The residue was dissolved in dichloromethaneand placed on a silica gel column. The column was eluted with 5%methanol in dichloromethane and then with 10% methanol indichloromethane. The 10% methanol in dichloromethane fractions werecombined and concentrated under vacuum to provideN¹-[4-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamide asa solid, m.p. 174-175° C. ¹H NMR (500 MHz, DMSO-d₆) δ8.48 (t, J=6.0 Hz,1H), 8.00 (d, J=8.0 Hz, 1H), 7.78 (d, J=8.0 Hz, 2H), 7.60 (d, J=8.0 Hz,1H), 7.50 (t, J=8.0 Hz, 1H), 7.43 (t, J=8.0 Hz, 2H), 7.39 (t, J=8.0 Hz,1H), 7.18 (t, J=8.0 Hz, 1H), 6.50 (broad s, 2H), 4.54 (t, J=7.0 Hz, 2H),3.32 (m, 2H), 2.91 (t, J=7.0 Hz, 2H), 1.86 (quintet, J=7.0 Hz, 2H), 1.77(quintet, J=7.0 Hz, 2H), 1.70 (quintet, J=7.0 Hz, 2H), 1.41 (sextet,J=7.0 Hz, 2H), 0.91 (t, J=7.0 Hz, 3H); MS (CI) m/e 416 (M+H).

EXAMPLE 7N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-(chloromethyl)benzamide

Part A

Oxalyl chloride (4.4 mL of 2M in chloroform, 8.8 mmol) was added to asuspension of 4-(chloromethyl)benzoic acid (1 g, 5.7 mmol) indichloromethane. N,N-dimethylformamide (4 drops) was added to catalyzethe reaction. After 1 hour analysis by HPLC indicated 100% cleanconversion. The reaction mixture was concentrated under vacuum toprovide 4-(chloromethyl)benzoyl chloride.

Part B

A solution of 4-(chloromethyl)benzoyl chloride (1.06 g, 5.6 mmol) indichloromethane was added to a suspension of1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (1.0 g, 3.9 mmol) inpyridine (250 mL). After 1 hour HPLC analysis indicated that thereaction was complete. The reaction mixture was concentrated undervacuum. The residue was combined with saturated aqueous sodiumbicarbonate. A solid was isolated by filtration then dissolved inchloroform containing a small amount of methanol. The solution waswashed with saturated aqueous sodium bicarbonate. The organic layer wasconcentrated under vacuum. The resulting residue was purified by columnchromatography (silica gel eluting with 10% methanol in dichloromethane)to provideN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-(chloromethyl)benzamideas a solid, m.p. 240-300 (dec.). ¹H NMR (500 MHz, DMSO-d₆) δ8.49 (t,J=6.0 Hz, 1H), 8.21 (s, 1H), 8.03 (d, J=8.0 Hz, 1H), 7.76 (d, J=8.0 Hz,2H), 7.61 (d, J=8.0 Hz, 1H), 7.46 (d, J=8.0 Hz, 2H), 7.42 (t, J=8.0 Hz,1H), 7.20 (t, J=8.0 Hz, 1H), 6.80 (broad s, 2H), 4.78 (s, 2H), 4.62 (t,J=7.0 Hz, 2H), 3.28 (q, J=6.0 Hz, 2H), 1.89 (quintet, J=7.0 Hz, 2H),1.56 (quintet, J=7.0 Hz, 2H); MS (CI) m/e 408 (M+H).

EXAMPLE 8N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-[(2-tetrahydro-1H-1-pyrrolyl-1H-benzo[d]imidazol-1-yl)methyl]benzamide

Part A

2-Hydroxy-1H-benzimidazole (62 g, 0.46 mole) was added to phosphorousoxychloride (200 mL) and the mixture was refluxed for 4.5 hours. Theresulting solution was poured over 4 L of ice and the mixture was madestrongly basic with ammonium hydroxide. The resulting solid was isolatedby filtration, washed with water and dried to provide crude2-chloro-1H-benzimidazole.

Part B

2-Chloro-1H-benzimidazole (10.0 g, 0.066 mol), pyrrolidine (18.5 g, 0.26mol), and ethanol (100 mL) were combined. The resulting solution washeated at 160-170° C. for 6 hours and then the solvent was evaporated.The resulting residue was mixed with water. The mixture was madestrongly acidic with hydrochloric acid and then made basic with ammoniumhydroxide. The resulting solid was isolated by filtration, washed withwater and then air dried to provide 11.8 g of crude product as a tanpowder. This material was recrystallized from ethyl acetate/methanol toprovide 4.9 g of 2-pyrrolidino-1H-benzimidazole. Analysis: Calculatedfor C₁₁H₁₃N₃: %C, 70.56; %H, 7.00; %N, 22.44; Found: %C, 70.13; %H,7.05; %N, 22.70.

Part C

Sodium hydride (402 mg, 11 mmol) was added to a suspension of2-pyrrolidino-1H-benzimidazole (1.9 g, 10.1 mmol) in dryN,N-dimethylformamide (30 mL). All solids dissolved. The solution wasallowed to stir at ambient temperature for 15 minutes following thecessation of foaming. The solution was cooled to 5° C. and a solidformed. Methyl 4-(bromomethyl)benzoate (2.1 g, 01 mol) was added to thesuspension and all the solids dissolved. The solution was allowed tostir at ambient temperature and a solid formed. The mixture was stirredat ambient temperature overnight and then it was poured into cold water.A solid was isolated by filtration, washed with water and dried toprovide 3.0 g of crude product as an off-white solid. This material wasrecrystallized from methanol to provide methyl4-[(2-pyrrolidinyl-1H-benzimidazol-1yl)methyl]benzoate. Analysis:Calculated for C₂₀H₂₁N₃O₂: %C, 71.62; %H, 6.31; %N, 12.53; Found: %C,71.44; %H, 6.41; %N, 12.50.

Part D

Methyl 4-[(2-pyrrolidinyl-1H-benzimidazol-1yl)methyl]benzoate (2.5 g,7.5 mmol) was added to a solution of sodium hydroxide (1.8 g, 45 mmol)in water (30 mL) and methanol (10 mL). The mixture was heated on a steambath until all of the ester dissolved. Heating was continued for anadditional 15 minutes and then the solution was diluted with an equalvolume of water and neutralized with hydrochloric acid. The resultingprecipitate was isolated by filtration, washed with water and dried toprovide 1.9 g of crude product. This material was recrystallized fromN,N-dimethylformamide to provide4-[(2-pyrrolidinyl-1H-benzimidazol-1yl)methyl]benzoic acid. Analysis:Calculated for C₁₉H₁₉N₃O₂: %C, 71.01; %H, 5.96; %N, 13.07; Found: %C,70.01; %H, 6.14; %N, 13.32.

Part E

Oxalyl chloride (4 mL) was added to a suspension of4-[(2-pyrrolidinyl-1H-benzimidazol-1yl)methyl]benzoic acid (0.28 g,0.872 mmol) in chloroform (50 mL). The mixture was heated at reflux for1 hour and then concentrated under vacuum. The residue was diluted withtoluene, concentrated under vacuum and then dried under vacuum atambient temperature over the weekend to provide crude4-[(2-pyrrolidinyl-1H-benzimidazol-1yl)methyl]benzoyl chloride.

Part F

1-(4-Aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.20 g, 0.783 mmol)was added to a mixture of the acid chloride from Part E and pyridine (20mL). After 10 minutes analysis by HPLC indicated that the reactionmixture contained product plus about 10% each of the acid chloride andthe amine. The reaction mixture was concentrated under vacuum. Theresidue was combined with water, treated with 0.1 N sodium hydroxide andthen extracted with dichloromethane. The dichloromethane extract waspurified by column chromatography (silica gel eluting with 5-10%methanol in dichloromethane) to provideN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-[(2-tetrahydro-1H-1-pyrrolyl-1H-benzo[d]imidazol-1-yl)methyl]benzamideas a solid, m.p. 150-153° C. MS (EI) m/e 558.2865 (558.2855 calcd forC₃₃H₃₄N₈O).

EXAMPLE 9N¹-[5-(4-Amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)pentyl]benzamide

Part A

Under an argon atmosphere, 1,5-diaminopentane (25 g, 0.24 mol) andbenzamide (9.9 g, 0.081 mol) were combined and heated at refluxovernight. The reaction mixture was concentrated under vacuum to removethe excess diamine. The residue was distilled at about 210° C. at 12torr (16×10² pascals) to provide 11.8 g of N-(5-aminopentyl)benzamide asa colorless oil.

Part B

Triethylamine (1 eq.) was added to a suspension of4-chloro-3-nitroquinoline hydrochloride (13 g, 53 mmol) in chloroform. Asuspension of N-(5-aminopentyl)benzamide (11 g, 53 mmol) in chloroformwas added and the reaction mixture was heated to reflux. Progress of thereaction was monitored by HPLC. The reaction mixture was concentratedunder vacuum. The residue was diluted with toluene, heated to reflux andthen filtered while still hot. The filtrate was allowed to cool. Theresulting precipitate was isolated by filtration to provide 16.9 g ofN¹-{5-[(3-nitroquinolin-4-yl)amino]pentyl}benzamide as a yellow solid,m.p. 130-132° C. ¹H NMR (500 MHz, DMSO-d₆) δ9.07 (s, 1H), 9.02 (broad s,1H), 8.53 (d, J=8.0 Hz, 1H), 8.43 (t, J=6.0 Hz, 1H), 7.89 (dd, J=8.0,1.2 Hz, 1H), 7.83 (dt, J=8.0, 1.2 Hz, 1H), 7.80 (d, J=8.0 Hz, 2H), 7.57(dt, J=8.0, 1.2 Hz, 1H), 7.50 (t, J=8.0 Hz, 1H), 7.43 (t, J=8.0 Hz, 2H),3.63 (q, J=6.0 Hz, 2H), 3.25 (q, J=6.0 Hz, 2H), 1.77 (quintet, J=7.0 Hz,2H), 1.55 (quintet, J=7.0 Hz, 2H), 1.39 (quintet, J=7.0 Hz, 2H).

Part C

A catalytic amount of platinum on carbon was added to a suspension ofN¹-{5-[(3-nitroquinolin-4-yl)amino]pentyl}benzamide (3.4 g, 9 mmol) inisopropyl alcohol (250 mL). The reaction mixture was placed under ahydrogen atmosphere at 50 psi (3.4×10⁴ pascals) on a Parr apparatus.After 2 hours the reaction mixture was filtered to remove the catalyst.The filtrate was concentrated under vacuum to provide crudeN¹-{5-[(3-aminoquinolin-4-yl)amino]pentyl}benzamide. This material wascombined with triethylorthoacetate (1.4 g, 9 mmol) and toluene (200 mL).The reaction mixture was heated overnight on a steam bath with a Vigreuxcolumn. The toluene was decanted from the reaction mixture andconcentrated under vacuum to provideN¹-[5-(2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)pentyl]benzamide as anoil.

Part D

3-Chloroperoxybenzoic acid (3 g, 9 mmol) was added to a solution of theoil from Part C in methyl acetate (50 mL). The reaction mixture wasstirred at ambient temperature overnight and then diluted with diethylether (50 mL). The resulting precipitate was isolated by filtration andthen washed with diethyl ether to provide 1.6 g of1-(5-benzamidopentyl)-2-methyl-1H-imidazo[4,5-c]quinoline-5N-oxide.

Part E

Ammonium hydroxide (50 mL) was added to a solution of1-(5-benzamidopentyl)-2-methyl-1H-imidazo[4,5-c]quinoline-5N-oxide (1.6g, 4.12 mmol) in dichloromethane (150 mL). Tosyl chloride (0.78 g, 4.12mmol) was slowly added with rapid stirring of the reaction mixture.After 1 hour the organic layer was separated, washed with 1% sodiumcarbonate and then concentrated under vacuum. The resulting residue wascombined with 1N hydrochloric acid (30 mL), treated with charcoal andthen filtered. The filtrate was neutralized. An oil precipitated out.The oil solidified overnight to provide 0.63 g ofN¹-[5-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)pentyl]benzamideas a solid, m.p. 110-120° C. ¹H NMR (500 MHz, DMSO-d₆) δ8.50 (t, J=5.5Hz, 1H), 8.12(d, J=8.0 Hz, 1H), 7.82 (d, J=8.5 Hz, 2H), 7.71 (d, J=8.5Hz, 1H), 7.63 (broad s, 2H), 7.55 (t, J=8.5 Hz, 1H), 7.51 (t, J=8.3 Hz,1H), 7.46 (t, J=8.0 Hz, 2H), 7.40 (t, J=8.0 Hz, 1H), 4.52 (t, J=7.5 Hz,2H), 3.28 (q, J=6.0 Hz, 2H), 2.64 (s, 3H), 1.87 (quintet, J=7.0 Hz, 2H),1.79 (quintet, J=7.0 Hz, 2H), 1.48(quintet, J=7.0 Hz, 2H); MS (CI) m/e388 (M+H).

EXAMPLE 10N¹-[5-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)pentyl]benzamideHydrochloride

Part A

A catalytic amount of platinum on carbon was added to a suspension ofN¹-{5-[(3-nitroquinolin-4-yl)amino]pentyl}benzamide (5 g, 13.2 mmol) intoluene (250 mL). The reaction mixture was placed under a hydrogenatmosphere at 50 psi (3.4×10⁴ pascals) on a Parr apparatus. After about2 hours an oily ball had formed in the bottom of the Parr bottle.Magnesium sulfate and additional catalyst were added and thehydrogenation was continued overnight. The reaction mixture was filteredto remove the catalyst. The residue in the Parr bottle was combined withisopropyl alcohol (150 mL), heated on a steam bath and then filtered.HPLC analysis indicated that both filtrates contained product so theywere combined and concentrated under vacuum to provide crudeN¹-{5-[(3-aminoquinolin-4-yl)amino]pentyl}benzamide. This material wascombined with toluene (250 mL). Triethylorthoformate (4 g, 26.4 mmol)was added and the reaction mixture was heated at reflux with a Vigreuxcolumn for 2 hours. The reaction mixture was allowed to cool to ambienttemperature. The resulting precipitate was isolated by filtration toprovide 3.4 g of N¹-[5-(1H-imidazo[4,5-c]quinolin-1-yl)pentyl]benzamideas a solid, m.p. 171.5-172.5° C. ¹H NMR (500 MHz, DMSO-d₆) δ9.22 (s,1H), 8.43 (t, J=6.0 Hz, 2H), 8.38 (m, 1H), 8.18 (m, 1H), 7.80 (d, J=7.0Hz, 2H), 7.73 (m, 2H), 7.51 (t, J=7.0 Hz, 1H), 7.45 (t, J=7.0 Hz, 2H),4.72 (t, J=7.5 Hz, 2H), 3.25 (q, J=6.0 Hz, 2H), 1.94 (quintet, J=7.5 Hz,2H), 1.58 (quintet, J=7.5 Hz, 2H), 1.40 (quintet, J=8.5 Hz, 2H).

Part B

3-Chloroperoxybenzoic acid (1.9 g, 5.58 mmol) was added to a solution ofN¹-[5-(1H-inmidazo[4,5-c]quinolin-1-yl)pentyl]benzamide (2.0 g, 5.58mmol) in chloroform. After 4 hours HPLC analysis indicated that thereaction was complete. The reaction was washed twice with 1% sodiumcarbonate (50 mL) and then concentrated under vacuum to provide1-(5-benzamidopentyl)-1H-imidazo[4,5-c]quinoline-5N-oxide.

Part C

Ammonium hydroxide was added to a solution of1-(5-benzamidopentyl)-1H-imidazo[4,5-c]quinoline-5N-oxide (2.1 g, 5.58mmol) in dichloromethane. Tosyl chloride (1.06 g, 5.58 mmol) was slowlyadded with rapid stirring of the reaction mixture. After 1 hour thereaction was diluted with dichloromethane. The organic layer wasseparated, washed with 1% sodium carbonate and then concentrated undervacuum. The resulting residue was dissolved in isopropyl alcohol (100mL) and then 6N hydrochloric acid (0.93 mL) was added. The resultingprecipitate was suspended in water (150 mL), heated to reflux, treatedwith charcoal and then filtered. The filtrate was allowed to cool. Theresulting precipitate was isolated by filtration and dried to provide0.9 g of N¹-[5-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)pentyl]benzamidehydrochloride as a white crystalline solid, m.p. 217-219° C. Analysis:Calculated for C₂₂H₂₃N₅O.HCl.1/2H₂O: %C, 52.85; %H, 6.85; %N, 14.01;Found: %C, 52.62; %H, 6.44%; %N, 13.87. ¹H NMR (500 MHz, DMSO-d₆) δ13.84(broad s, 1H), 9.24 (broad s, 2H), 8.51 (s, 1H), 8.43 (t, J=6.0 Hz, 1H),8.22 (d, J=8.0 Hz, 1H), 7.82 (d, J=8.0 Hz, 1H), 7.76 (d, J=8.0 Hz, 2H),7.70 (t, J=8.0 Hz, 1H), 7.56 (t, J=8.0 Hz, 1H), 7.49 (t, J=8.0 Hz, 1H),7.42 (t, J=8.0 Hz, 2H), 4.66 (t, J=7.0 Hz, 2H), 3.23 (q, J=6.0 Hz, 2H),1.90 (quintet, J=7.0 Hz, 2H), 1.56 (quintet, J=7.0 Hz, 2H), 1.38(quintet, J=7.0 Hz, 2H); MS (CI) m/e 374 (M+H).

EXAMPLE 11N¹-[3-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)propyl]benzamideHydrochloride

Part A

Benzamide (25 g, 0.20 mol) and 1,3-diaminopropane (45.9 g, 0.60 mol)were combined in a Parr vessel and heated to 150° C. for 15 hours. Thevessel was cooled and the reaction mixture was concentrated under vacuumto remove excess diamine. The residue was dissolved in water (500 mL)and concentrated hydrochloric acid was added to adjust the pH to <1. Theresulting precipitate (starting benzamide and diacylated product) wasremoved by filtration. The filtrate was washed with dichloromethane. Theaqueous layer was made strongly basic by the addition of 50% sodiumhydroxide and then it was extracted with dichloromethane (4×300 mL). Theextracts were combined, washed with brine (300 mL), dried over sodiumsulfate and then concentrated under vacuum to provide 11.9 g ofN-(3-aminopropyl)benzamide as an oil.

Part B

Triethylamine (9.3 mL, 67 mmol) was added to a mixture of4-chloro-3-nitroquinoline hydrochloride (16.4 g, 67 mmol) anddichloromethane (400 mL). A solution of N-(3-aminopropyl)benzamide (11.9g, 67 mmol) in dichloromethane (100 mL) was added all a once. Thereaction mixture was stirred at ambient temperature for 1 hour and thenheated on a steam bath for 1 hour. The resulting precipitate wasisolated by filtration to provide 6 g ofN¹-{3-[(3-nitroquinolin-4-yl)amino]propyl}benzamide as a yellow solid,m.p. 209-211° C. ¹H NMR (500 MHz, DMSO-d₆) δ9.07 (broad s, 1H), 9.05 (s,1H), 8.54 (t, J=6.0 Hz, 1H), 8.51 (d, J=8.0 Hz, 1H), 7.89 (d, J=8.0 Hz,1H), 7.82 (t, J=8.0 Hz, 1H), 7.76 (d, J=8.0 Hz, 2H), 7.55 (t, J=8.0 Hz,1H), 7.50 (t, J=8.0 Hz, 1H), 7.43 (t, J=8.0 Hz, 2H), 3.69 (q, J=6.0 Hz,2H), 3.35 (q, J=6.0 Hz, 2H), 2.00 (quintet, J=7.0 Hz, 2H).

Part C

A suspension of N¹-{3-[(3-nitroquinolin-4-yl)amino]propyl}benzamide (1.0g, 2.8 mmol) in isopropyl alcohol (120 mL) was warmed to dissolve someof the material. A catalytic amount of platinum on carbon was added andthe reaction mixture was placed under a hydrogen atmosphere at 50 psi(3.4×10⁴ pascals) on a Parr apparatus. After 3 hours the reactionmixture was filtered to remove catalyst. The filtrate was concentratedunder vacuum to provide crudeN¹-{3-[(3-aminoquinolin-4-yl)amino]propyl}benzamide as an oil. Toluene(100 mL) was added to the oil followed by the addition oftriethylorthoformate (0.8 g, 5.6 mmol). The reaction mixture was heatedon a steam bath overnight. The reaction mixture was allowed to cool toambient temperature. The resulting precipitate was isolated byfiltration to provide 0.53 g ofN¹-[3-(1H-imidazo[4,5-c]quinolin-1-yl)propyl]benzamide as an off whitesolid, m.p. 188-190° C. ¹H NMR (500 MHz, DMSO-d₆) δ8.67 (t, J=5.5 Hz,1H), 8.50 (s, 1H), 8.37 (d, J=7.5 Hz, 1H), 8.17 (dd, J=8.0, 1.5 Hz, 1H),7.87 (d, J=7.0 Hz, 2H), 7.71 (dt, J=7.5, 1.5 Hz, 1H), 7.56 (dt, J=7.5,1.0 Hz, 1H), 7.54 (d, J=8.0 Hz, 2H), 7.48 (t, J=7.0 Hz, 2H), 4.78 (t,J=7.0 Hz, 2H), 3.38 (q, J=6.0 Hz, 2H), 2.18 (quintet, J=7.0 Hz, 2H).

Part D

3-Chloroperoxybenzoic acid (0.55 g, 1.6 mmol) was slowly added atambient temperature to a solution ofN¹-[3-(1H-imidazo[4,5-c]quinolin-1-yl)propyl]benzamide (0.53 g, 1.6mmol) in chloroform (50 mL). After 3 hours the reaction was washed with1% sodium carbonate (2×30 mL) and then concentrated under vacuum toprovide 0.32 g of1-(3-benzamidopropyl)-1H-imidazo[4,5-c]quinoline-5N-oxide as a solid.

Part E

Ammonium hydroxide (20 mL) was added to a solution of1-(3-benzamidopropyl)-1H-imidazo[4,5-c]quinoline-5N-oxide (0.32 g, 0.92mmol) in dichloromethane (100 mL). Tosyl chloride (0.17 g, 0.92 mmol)was slowly added. The reaction mixture was stirred overnight at ambienttemperature and then it was concentrated under vacuum to remove thedichloromethane. The resulting precipitate was isolated by filtrationand then washed with water. This material was dissolved in isopropylalcohol (20 mL/g). Concentrated hydrochloric acid (1 eq.) was added andthen the volume of the reaction mixture was reduced by 10-20%. Theresulting precipitate was isolated by filtration and washed withisopropyl alcohol to provide 0.25 g ofN¹-[3-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)propyl]benzamidehydrochloride as a solid, m.p. 265-270° C. Analysis: Calculated forC₂₀H₁₉N₅O.HCl.1/2H₂O: %C, 61.46; %H, 5.42; %N, 17.92; Found: %C, 61.79;%H, 5.34; %N, 17.61. ¹H NMR (500 MHz, DMSO-d₆) δ13.74 (broad s, 1H),9.30 (broad s, 2H), 8.73 (t, J=6.0 Hz, 1H), 8.61 (s, 1H), 8.22 (d, J=8.0Hz, 1H), 7.87 (d, J=8.0 Hz, 2H), 7.84 (d, J=8.0 Hz, 1H), 7.71 (t, J=8.0Hz, 1H), 7.54 (t, J=8.0 Hz, 1H), 7.48 (t, J=8.0 Hz, 2H), 7.43 (t, J=8.0Hz, 1H), 4.75 (t, J=7.0 Hz, 2H), 3.39 (q, J=6.0 Hz, 2H), 217 (t, J=7.0Hz, 2H); MS (EI) m/e 345.1593 (345.1590 calcd for C₂₀H₁₉N₅O).

EXAMPLE 12N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-morpholinonicotinamide

Part A

Carbonyl diimidazole (18.6 g, 0.115 mol) was added to a suspension of6-chloronicotinic acid (16.6 g, 0.105 mol) in dichloromethane (250 mL).After all of the solid had dissolved the reaction solution was stirredat ambient temperature for 1 hour and then isopropyl alcohol (100 mL)was added. The dichloromethane was removed under vacuum. A catalyticamount of sodium isopropoxide was added to the solution and the solutionwas heated at reflux for 1 hour. The solution was then concentratedunder vacuum. The resulting residue was slurried with water and thenextracted with diethyl ether. The extract was dried over magnesiumsulfate and then concentrated under vacuum to provide 23.9 g ofisopropyl 6-chloronicotinate.

Part B

A solution of isopropyl 6-chloronicotinate (6.0 g, 0.03 mol) andmorpholine (13 mL, 0.15 mol) in isopropyl alcohol (60 mL) was heated atreflux for 72 hours. The solution was allowed to cool to ambienttemperature overnight. The resulting precipitate was isolated byfiltration, washed with isopropyl alcohol and dried to provide isopropyl6-morpholinonicotinate. The filtrate was diluted with water. Theresulting precipitate was isolated by filtration, washed with water anddried to provide isopropyl 6-morpholinonicotinate. The combined yieldwas 8.3 g. The isopropyl 6-morpholinonicotinate was combined with 1 Nsodium hydroxide (40 mL) and the resulting suspension was stirred at50-60° C. until all of the solid had dissolved. The solution was stirredat ambient temperature overnight during which time a precipitate formed.This material was isolated by filtration and identified as startingmaterial. The filtrate was neutralized with concentrated hydrochloricacid. The resulting precipitate was isolated by filtration, washed withwater and dried to provide 3.3 g of crude product. This material wasrecrystallized from methanol/dichloromethane to provide6-morpholinonicotinic acid as a solid, m.p. 259-261° C. Analysis:Calculated for C₁₀H₁₂N₂O₃: %C, 57.19; %H, 5.81; %N, 13.48; Found: %C,57.50; %H, 5.71; %N, 13.53.

Part C

N,N-Dimethylformamide (1 mL) was slowly added to a solution of oxalylchloride (0.13 g, 1 mmol) in chloroform (5 mL). 6-Morpholinonicotinicacid (0.21 g, 1 mmol) was added and the reaction mixture was stirred for15 minutes. The reaction mixture was concentrated under vacuum, dilutedwith toluene and then concentrated under vacuum to provide6-morpholinonicotinoyl chloride. This material was kept under vacuum atambient temperature overnight and then used in the next step.

Part D

The acid chloride from Part C was dissolved in pyridine (20 mL) and thenadded all at once to a warm solution of1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.25 g, 1 mmol) inpyridine (25 mL). The reaction mixture was concentrated under vacuum at40° C. to remove the pyridine. The resulting residue was combined withwater and 1N sodium hydroxide (25 mL). The mixture was extracted withdichloromethane. The extract was concentrated under vacuum. Theresulting residue was recrystallized from isopropyl alcohol to provideN³-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-morpholinonicotinamideas a solid, m.p. 160-170° C. (dec.). ¹H NMR (500 MHz, DMSO-d₆) δ8.55 (d,J=2.5 Hz, 1H), 8.52 (s, 1H), 8.28 (t, J=6.0 Hz, 1H), 8.22 (d, J=8.0 Hz,1H), 7.90 (dd, J=8.0, 2.5 Hz, 1H), 7.82 (d, J=8.0 Hz, 1H), 7.69 (t,J=8.0 Hz, 1H), 7.52 (d, J=8.0 Hz, 1H), 6.82 (d, J=8.0 Hz, 1H), 4.70 (t,J=7.0 Hz, 2H), 3.69 (t, J=5.0 Hz, 4H), 3.54 (t, J=5.0 Hz, 4H), 3.27 (q,J=6.0 Hz, 2H), 1.91(quintet, J=7.0 Hz, 2H), 1.58 (t, J=6.0 Hz, 2H); MS(EI) m/e 445.2209 (445.2226 calcd for C₂₄H₂₇N₇O₂).

EXAMPLE 13 N¹-[2-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]benzamide

Part A

Triethylamine (66.8 g, 0.33 mol) was added to a solution of tert-butylN-(2-aminoethyl)carbamate (55.0 g, 0.34 mol) in anhydrousdichloromethane (500 mL). 4-Chloro-3-nitroquinoline was slowly added andthe reaction exothermed. The reaction mixture was allowed to stir atambient temperature overnight. The resulting precipitate was isolated byfiltration to provide product as a yellow solid. The filtrate was washedwith water, dried over magnesium sulfate and then concentrated undervacuum. The resulting residue was slurried with hexane and filtered toprovide additional product as a yellow solid. The two crops werecombined to provide 101 g of tert-butylN-[2-(3-nitroquinolin-4-yl)aminoethyl]carbamate as a yellow solid, m.p.157-158.

Part B

Platinum on carbon (1 g of 10%) and sodium sulfate (2 g) were added to aslurry of tert-butyl N-[2-(3-nitroquinolin-4-yl)aminoethyl]carbamate(100 g, 0.30 mol) in toluene (500 mL). The mixture was placed under ahydrogen atmosphere at 50 psi (3.4×10⁴ pascals) on a Parr apparatus atambient temperature overnight. The reaction mixture was filtered. Thefiltrate was concentrated to provide 73 g of tert-butylN-[2-(3-aminoquinolin-4-yl)aminoethyl]carbamate as a dark gold oil.

Part C

Triethyl orthoformate (11.3 g, 73.4 mmol) was added to a solution oftert-butyl N-[2-(3-aminoquinolin-4-yl)aminoethyl]carbamate (21 g, 69.4mmol) in anhydrous toluene (250 mL). The reaction mixture was heated atreflux for 5 hours and then allowed to slowly cool to ambienttemperature. The resulting precipitate was isolated by filtration anddried to provide 17.6 g of tert-butylN-[2-(1H-imidazo[4,5-c]quinolin-1-yl)ethyl]carbamate as a light tansolid, m.p. 154-155° C.

Part D

3-Chloroperoxybenzoic acid (17.4 g, 60.6 mmol) was added in smallportions to a solution of tert-butylN-[2-(1H-imidazo[4,5-c]quinolin-1-yl)ethyl]carbamate (17.2 g, 55.1 mmol)in chloroform (250 mL). The reaction was maintained at ambienttemperature overnight and then quenched with 5% sodium carbonatesolution. The layers were separated. The organic layer was dried overmagnesium sulfate and then concentrated under vacuum to provide 15.0 gof 1-[2-(tert-butylcarbamyl)ethyl]-1H-imidazo[4,5-c]quinoline-5N-oxideas an off white solid, m.p. 213-215° C.

Part E

Trichloroacetyl isocyanate (9.5 g, 50.2 mmol) was slowly added to astirred solution of1-[2-(tert-butylcarbamyl)ethyl]-1H-imidazo[4,5-c]quinoline-5N-oxide(15.0 g, 45.7 mmol) in chloroform (200 mL). After 2 hours the reactionwas quenched with concentrated ammonium hydroxide (100 mL). Water (100mL) was added and the layers were separated. The aqueous layer wasextracted with chloroform. The organic layers were combined, dried overmagnesium sulfate and then concentrated under vacuum to provide a whitesolid. This material was slurried in warm methyl acetate and thenfiltered to provide 15 g of tert-butylN-[2-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]carbamate as a whitesolid, m.p. 215° C. ¹H NMR (500 MHz, DMSO-d₆) δ8.13 (t, J=8.0 Hz, 1H),8.03 (s, 1H), 7.61(d, J=8.0 Hz, 1H), 7.44 (t, J=8.0 Hz, 1H), 7.23 (t,J=8.0 Hz, 1H), 7.06 (t, J=6.0 Hz, 1H), 6.56 (broad s, 2H), 4.63 (t,J=7.0 Hz, 2H), 3.43 (q, J=6.0 Hz, 2H), 1.32 (s, 9H); MS (EI) m/e327.1696 (327.1695 calcd for C₁₇H₂₁N₅O₂)

Part F

Tert-butyl N-[2-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]carbamate(14.8 g, 45.2 mmol), trifluoroacetic acid (100 mL) and acetonitrile (100mL) were combined and maintained at ambient temperature overnight. Theacetonitrile was removed and the reaction mixture was heated at refluxfor 2 hours. The reaction mixture was concentrated under vacuum toprovide a tan solid. This material was dissolved in a minimal amount ofhot water. The solution was adjusted to pH 14 and allowed to cool. Thesolution was concentrated under vacuum. The resulting residue wasextracted with refluxing ethanol. The ethanol extract was concentratedunder vacuum to provide 3.0 g of1-(2-aminoethyly-1H-imidazo[4,5-c]quinolin-4-amine as a tan solid, m.p.265° C. ¹H NMR (500 MHz, DMSO-d₆) δ8.14 (s, 1H), 8.08 (dd, J=8.0, 1.5Hz, 1H), 7.62 (dd, J=8.0, 1.5 Hz, 1H), 7.44 (dt, J=8.0, 1.5 Hz, 1H),7.25 (dt, J=8.0, 1.5 Hz, 1H), 6.58 (broad s, 2H), 4.54 (t, J=7.0 Hz,2H), 3.01 (t, J=7.0 Hz, 2H), 1.60 (broad s, 2H); MS (EI) m/e227.1171(227.1171 calcd for C₁₂H₁₃N₅).

Part G

A mixture of 1-(2-aminoethyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.40 g,1.76 mmol) and anhydrous pyridine (60 mL) was heated until a clearsolution was obtained. The solution was then cooled with an ice bath.Benzoyl chloride (0.25 g, 1.76 mmol) was added. The reaction mixture wasmaintained at ambient temperature overnight and then concentrated undervacuum. The residue was slurried with water (200 mL) and a solid wasisolated by filtration. This material was recrystallized from isopropylalcohol to provide 0.15 g ofN¹-[2-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]benzamide as a whitepowder, m.p. 295° C. ¹H NMR (500 MHz, DMSO-d₆) δ8.50 (t, J=6.0 Hz, 1H),8.23 (d, J=8.0 Hz, 1H), 8.04 (s, 1H), 7.75(d, J=8.0 Hz, 2H), 7.64 (d,J=8.0 Hz, 1H), 7.49 (t, J=8.0 Hz, 1H), 7.43 (t, J=8.0, 1H), 7.41 (t,J=8.0 Hz, 2H), 7.25 (t, J=8.0 Hz, 1H), 6.28 (broad s, 2H), 4.80(t, J=7.0Hz, 2H), 3.80(q, J=6.0 Hz, 2H); MS (EI) m/e 331.1429 (331.1433 calcd forC₁₉H₁₇N₅O).

EXAMPLE 14N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-phenoxybenzamide

Under a nitrogen atmosphere, a mixture of1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.125 g, 0.49 mmol)and anhydrous pyridine (40 mL) was warmed with a heat gun to dissolvethe solid. The resulting solution was allowed to cool to ambienttemperature. A solution of 2-phenoxybenzoyl chloride (0.11 g, 0.47 mmol)in pyridine (5 mL) was added. The reaction mixture was maintained atambient temperature for 18 hours and then concentrated under vacuum. Theresulting solid residue was purified by flash chromatography (silica geleluting with 9:1 dichloromethane:methanol) to provide 0.12 g ofN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-phenoxybenzamideas a white solid, m.p. 93-94° C. ¹H NMR (500 MHz, DMSO-d₆) δ8.23 (t,J=6.0 Hz, 1H), 8.14 (s, 1H), 8.00 (d, J=8.0 Hz, 1H), 7.62 (d, J=8.0 Hz,1H), 7.54 (dd, J=8.0, 1.5 Hz, 1H), 7.43 (dt, J=8.0, 1.5 Hz, 1H), 7.42(dt, J=8.0, 1.5 Hz, 1H), 7.30 (t, J=8.0 Hz, 2H), 7.22 (t, J=8.0 Hz, 1H),7.18 (t, J=8.0 Hz, 1H), 7.07 (t, J=8.0 Hz, 1H), 6.89 (m, 3H), 6.59(broad s, 2H), 4.55 (t, J=7.0 Hz, 2H), 3.23 (q, J=6.0 Hz, 2H), 1.81(quintet, J=7.0 Hz, 2H), 1.47 (quintet, J=7.0 Hz, 2H); MS (EI) m/e451.2004 (451.2008 calcd for C₂₇H₂₅N₅O₂).

EXAMPLE 15N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-3-benzoylbenzamide

Using the method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.2 g, 0.78 mmol)was reacted with 3-benzoylbenzoyl chloride (0.18 g, 0.73 mmol) toprovide 0.19 g ofN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-3-benzoylbenzamideas a white crystalline solid, m.p. 103-105° C. ¹H NMR (500 MHz, DMSO-d₆)δ8.70 (t, J=6.0 Hz, 1H), 8.22 (s, 1H), 8.16 (broad s, 1H), 8.08 (d,J=8.0 Hz, 1H), 8.03 (d, J=8.0 Hz, 1H), 7.85 (d, J=8.0 Hz, 1H), 7.73 (d,J=8.0 Hz, 2H), 7.70 (t, J=8.0 Hz, 1H), 7.64 (t, J=8.0 Hz, 1H), 7.61 (d,J=8.0 Hz, 1H), 7.57 (t, J=8.0 Hz, 2H), 7.40 (t, J=8.0 Hz, 1H), 7.19 (t,J=8.0 Hz, 1H), 6.67 (broad s, 2H), 4.63 (t, J=7.0 Hz, 2H), 3.32 (q,J=6.0 Hz, 2H), 1.91 (quintet, J=7.0 Hz, 2H), 1.59 (quintet, J=7.0 Hz,2H); MS (EI) m/e 463.2022 (463.2008 calcd for C₂₈H₂₅N₅O₂).

EXAMPLE 16N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-3-phenylpropanamide

Using the method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.2 g, 0.78 mmol)was reacted with hydrocinnamoyl chloride (0.11 mL, 0.74 mmol) to provide0.14 g ofN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-3-phenylpropanamideas a white solid, m.p. 148-150° C. ¹H NMR (500 MHz, DMSO-d₆) δ8.19 (s,1H), 8.03 (d, J=8.0 Hz, 1H), 7.82 (t, J=6.0 Hz, 1H), 7.63 (d, J=8.0 Hz,1H), 7.45 (t, J=8.0 Hz, 1H), 7.27 (t, J=8.0 Hz, 1H), 7.22 (t, J=8.0 Hz,2H), 7.15 (m, 3H), 6.66 (broad s, 2H), 4.58 (t, J=7.0 Hz, 2H), 3.06 (q,J=6.0 Hz, 2H), 2.75 (t, J=7.0 Hz, 2H), 2.31 (t, J=7.0 Hz, 2H), 1.79(quintet, J=7.0 Hz, 2H), 1.40 (t, J=7.0 Hz, 2H); MS (EI) m/e 387.2067(387.2059 calcd for C₂₃H₂₅N₅O).

EXAMPLE 17N¹-[2-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-3-phenylpropanamide

Using the method of Example 14,1-(2-aminoethyl)-1H-imidazo[4,5-c]quinolin-4-amine (100 mg, 0.44 mmol)was reacted with hydrocinnamoyl chloride (0.065 mL, 0.44 mmol) toprovide 0.06 g ofN¹-[2-(4-amino-1H-imidazo[4,5-c]quiolin-1-yl)ethyl]-3-phenylpropanamideas a white solid, m.p. 254-256° C. ¹H NMR (500 MHz, DMSO-d₆) δ8.16 (d,J=8.0 Hz, 1H), 8.07 (t, J=6.0 Hz, 1H), 7.97 (s, 1H), 7.62 (dd, J=8.0,1.0 Hz, 1H), 7.45 (dt, J=8.0, 1.0 Hz, 1H), 7.26 (m, 3H), 7.16 (m, 3H),6.6 (broad s, 2H), 4.61 (t, J=7.0 Hz, 2H), 3.54 (q, J=6.0 Hz, 2H), 2.75(t, J=7.0 Hz, 2H), 2.31 (t, J=7.0 Hz, 2H), MS (EI) m/e 359.1745(359.1746 calcd for C₂₁H₂₁N₅O).

EXAMPLE 18N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-(4-benzoylphenoxy)acetamide

1-(4-Aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (99.6 mg, 0.39 mmol)and 2-(4-benzoylphenoxy)acetic acid (100 mg, 0.39 mmol) were combined inpyridine (10 mL). The mixture was warmed until homogeneous and thenallowed to cool. 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimidehydrochloride (82 mg, 0.43 mole) was added. The reaction mixture wasmaintained at ambient temperature overnight and then concentrated undervacuum. The residue was partitioned between chloroform and saturatedpotassium carbonate solution. The layers were separated. The aqueouslayer was extracted with chloroform. The organic layers were combined,dried over magnesium sulfate and then concentrated under vacuum toprovide a gold oil. The oil was purified by column chromatography(silica gel eluting with 10% methanol in dichloromethane) to provideabout 70 mg ofN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-(4-benzoylphenoxy)acetamideas a white solid, m.p. 73-98° C. ¹H NMR (500 MHz, DMSO-d₆) δ8.22 (t,J=6.0 Hz, 1H), 8.18 (s, 1H), 8.03 (d, J=8.3 Hz, 1H), 7.73 (d, J=8.0 Hz,2H), 7.68 (d, J=8.0 Hz, 2H), 7.65 (t, J=8.0 Hz, 1H), 7.60 (dd, J=8.0,1.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 2H), 7.42 (dt, J=8.0, 1.0 Hz, 1H), 7.25(t, J=8.0, 1.0 Hz, 1H), 7.07 (d, J=8.0 Hz, 2H), 6.58 (broad s, 2H), 4.61(t, J=7.0 Hz, 2H), 4.56 (s, 2H), 3.18 (q, J=6.0 Hz, 2H), 1.86 (quintet,J=7.0 Hz, 2H), 1.50 (quintet, J=7.0 Hz, 2H); MS (EI) m/e 493.2106(493.2114 calcd for C₂₉H₂₇N₅O₃).

EXAMPLE 19N-[4-Amino-1H-imidazo[4,5-c]quinolin-1-yl]butyl-5-[(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)oxy]pentamide

Using the general method of Example 18,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (100 mg, 0.392 mmol)was coupled with5-[(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)oxy]pentanoic acid (98.1mg, 0.392 mmol) to provide 20 mg ofN-[4-amino-1H-imidazo[4,5-c]quinolin-1-yl]butyl-5-[(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)oxy]pentamideas an off-white solid, m.p.150-157° C. ¹H NMR (500 MHz, DMSO-d₆) δ10.51(s, 1H), 10.36 (s, 1H), 8.23 (s, 1H), 8.05(d, J=8.0 Hz, 1H), 7.81 (t,J=6.0 Hz, 1H), 7.64 (t, J=6.0 Hz, 1H), 7.47 (t, J=8.0 Hz, 1H), 7.29 (t,J=8.0 Hz, 1H), 6.93 (broad s, 2H), 6.78(d, J=8.0 Hz, 1H), 6.48 (s, 1H),6.47 (d, J=8.0 Hz, 1H), 4.61 (t, J=7.0 Hz, 2H), 3.82 (broad s, 2H), 3.08(q, J=6.0 Hz, 2H), 2.05 (t, J=7.0 Hz, 2H), 1.84 (quintet, J=7.0 Hz, 2H),1.58 (broad s, 4H), 1.44 (quintet, J=7.0 Hz, 2H); MS (EI) m/e 487.2329(487.2332 calcd for C₂₆H₂₉N₇O₃).

EXAMPLE 20 N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolinl-yl)butyl]-4-benzoylbenzamide

Using the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.51 g, 2.0 mmol)was reacted with 4-benzoylbenzoyl chloride (2.0 mmol) to provide 0.15 gofN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolinl-yl)butyl]-4-benzoylbenzamideas a white solid, m.p. 159-161° C. ¹H NMR (500 MHz, CDCl₃) δ8.06 (s,1H), 7.96 (d, J=8.0 Hz, 1H), 7.91 (d, J=8.0 Hz, 1H), 7.85 (d, J=8.0 Hz,2H), 7.81 (d, J=8.0 Hz, 2H), 7.76 (d, J=8.0 Hz, 2H), 7.60 (m, 2H), 7.49(t, J=8.0 Hz, 2H), 7.48 (t, J=8.0 Hz, 1H), 7.24 (broad s, 1H), 6.86(broad s, 1H), 6.60 (t, J=6 Hz, 1H), 4.69 (t, J=7.0 Hz, 2H), 3.62 (q,J=6.0 Hz, 2H), 2.14 (quintet, J=7.0 Hz, 2H), 1.82 (quintet, J=7.0 Hz,2H); MS (EI) m/e 463.2002 (463.2008 calcd for C₂₈H₂₅N₅O₂).

EXAMPLE 21N⁶-[4-(4-Anino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-quinolinecarboxamide

Using the general method of Example 18,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.5 g, 1.96 mmol)was coupled with 6-quinolinecarboxylic acid (0.34 g, 1.96 mmol) toprovide 0.08 g ofN⁶-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-quinolinecarboxamideas a tan powder, m.p. 122-127° C. (foaming). ¹H NMR (300 MHz, DMSO-d₆)δ8.98 (m, 1H), 8.73 (t, J=5.4 Hz, 1H), 8.43 (m, 2H), 8.23 (s, 1H),8.13-8.03 (m, 3H), 7.60 (m, 2H), 7.40 (m, 1H), 7.20 (m, 1H), 6.58 (broads, 2H), 4.66 (t, J=6.7 Hz, 2H), 3.37 (m, 2H), 1.96 (m, 2H), 1.64 (m,2H); MS (EI) m/e 410.1847 (410.1855 calcd for C₂₄H₂₂N₆O).

EXAMPLE 22N¹-[3-(4-Amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]benzamide

Part A

Using the general method of Example 11 Part C,N¹-{3-[(3-nitroquinolin-4-yl)amino]propyl}benzamide (2.0 g, 5.7 mmol)was reduced to the diamine and then reacted with triethylorthoacetate toprovide 0.74 g ofN¹-[3-(2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]benzamide as asticky dark yellow solid.

Part B

Using the general method of Example 11 Part D, the material from Part Awas oxidized to provide 0.35 g of1-(3-benzamidopropyl)-2-methyl-1H-imidazo[4,5-c]quinoline-5N-oxide as asolid.

Part C

Ammonium hydroxide (20 mL) was added to a solution of1-(3-benzamidopropyl)-2-methy-1H-imidazo[4,5-c]quinoline-5N-oxide (0.35g, 0.97 mmol) in dichloromethane (100 mL). Tosyl chloride (0.185 g, 0.97mmol) was slowly added with vigorous stirring. The reaction mixture wasstirred overnight at ambient temperature and then it was concentratedunder vacuum to remove the dichloromethane. The resulting solid wasrecrystallized from dichloromethane to provide 0.1 g ofN¹-[3-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]benzamideas a solid, m.p. 230-231.4° C.

EXAMPLE 23 N¹-[6-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)hexyl]benzamide

Part A

Using the general method of Example 9 Part A, hexamethylenediamine(348.63 g, 3 mol) was reacted with benzamide (121.14 g, 1 mole) toprovide 136.5 g of N-(6-aminohexyl)benzamide.

Part B

Using the general method of Example 9 Part B, 4-chloro-3-nitroquinolinehydrochloride (10 g, 41 mnmol) was reacted withN-(6-aminohexyl)benzamide to provide 12.85 g ofN¹-{6-[(3-nitroquinolin-4-yl)amino]hexyl}benzamide as a yellowcrystalline solid.

Part C

Using the general method of Example 9 Part C, 12.3 g of the materialfrom part B was reduced and then reacted with triethylorthoformate (8.94g, 6 mmol) to provide 6.4 g ofN¹-[6-(1H-imidazo[4,5-c]quinolin-1-yl)hexyl]benzamide as a brown oil.

Part D

3-Chloroperoxybenzoic acid (5.9 g, 17 mmol) was slowly added to asolution of the material from Part C in chloroform. The solution turnedorange. After 2 hours the reaction mixture was washed twice with aqueoussodium carbonate and then concentrated under vacuum to provide 6.0 g of1-(6-benzamidohexyl)-1H-imidazo[4,5-c]quinoline-5N-oxide as an orangeoil.

Part E

Ammonium hydroxide was added to a solution of the material from Part Din dichloromethane. Tosyl chloride (2.94 g, 15 mmol) was slowly addedwith vigorous stirring. The reaction mixture was allowed to stir atambient temperature overnight and then it was concentrated under vacuum.The resulting crude material was recrystallized from propyl acetate toprovide 0.91 g ofN¹-[6-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)hexyl]benzamide as a beigecrystalline solid, m.p. 146-155° C.

EXAMPLE 24N¹-[4-(4-Amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentanamide

D-biotinyl N-hydroxysuccinimide (0.57 g, 1.67 mmol) was added to asolution of 1-(4-aminobutyl)-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine(0.52 g, 1.67 mmol) in pyridine (25 mL). The reaction was maintained atambient temperature overnight and then concentrated to dryness. Theresidue was partitioned between dichioromethane and aqueous saturatedpotassium carbonate. The organic layer was dried over magnesium sulfateand then concentrated to provide 0.4 g ofN¹-[4-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentamideas a solid, m.p. 214-215° C. Analysis: Calculated for C₂₈H₃₉N₇O₂S: %C,62.54; %H, 7.31; %N, 18.23; Found: %C, 61.67; %H, 7.37; %N, 17.62.

EXAMPLE 25N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentanamide

A solution of 1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.38g, 1.49 mmol) in pyridine (20 mL) was added to a solution ofN-hydroxysuccinimidobiotin (0.51 g, 1.49 mmol) in pyridine (20 mL). Thereaction was maintained at ambient temperature overnight and thenconcentrated to dryness. The residue was partitioned betweendichloromethane and aqueous saturated potassium carbonate. The organiclayer was dried over magnesium sulfate and then concentrated to provide0.58 g ofN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentamideas a solid, m.p. 104-106° C. High resolution mass spec: Theoreticalmass=481.2260, Measured mass=481.2261.

EXAMPLE 26N¹-[2-(4-Amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-5-(2-iminoperhydrothieno[3,4-d]imidazol-4-yl)pentanamide

A solution of N-hydroxysuccinimidoiminobiotin (0.74 g, 1.76 mmol) inpyridine (10 mL) was slowly added to a solution of1-(2-aminoethyl)-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine (0.50 g, 1.76mmol) in pyridine (30 mL). The reaction was maintained at ambienttemperature overnight and then concentrated to dryness. The residue waspartitioned between dichloromethane and aqueous saturated potassiumcarbonate. The organic layer was dried over magnesium sulfate and thenconcentrated to dryness. The residue was recrystallized from ethanol toprovide 0.5 g ofN¹-[2-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-5-(2-iminoperhydrothieno[3,4-d]imidazol-4-yl)pentanamideas a solid, m.p. 95-96° C. High resolution mass spec: Theoreticalmass=508.2733, Measured mass=508.2723.

EXAMPLE 27N¹-[2-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentanamide

Using the general method of Example 24, N-hydroxysuccinimidobiotin (0.6g, 1.76 mmol) was reacted with1-(2-aminoethyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.4 g, 1.76 mmol) toprovide 0.6 g ofN¹-[2-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentanamideas a solid, m.p. 169° C.

EXAMPLE 28N¹-[2-(4-Amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentanamide

Using the general method of Example 25,1-(4-aminoethyl)-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine (0.4 g, 1.47mmol) was reacted with N-hydroxysuccinimidobiotin (0.5 g, 1.47 mmol) toprovide 0.44 g ofN¹-[2-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentanamideas a white solid, m.p. 124-126° C. High resolution mass spec:Theoretical mass=509.25, Measured mass=509.2580.

EXAMPLE 29N¹-[2-(4-Amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentanamideDitrifluoroacetate

Triethylamine (1.2 g, 11.4 mmol) was added in a single portion to aslurry of1-(2-aminoethyl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-aminehydrochloride (3.39 g, 10.53 mmol) in chloroform (150 mL). The reactionmixture became clear. N-hydroxysuccinimidobiotin (3.0 g, 8.79 mmol) wasthen slowly added. After 2 hours the turbid reaction mixture was heatedto reflux. The reaction mixture was maintained at reflux overnight andbecame clear. The reaction mixture was allowed to cool to ambienttemperature and then it was quenched with water. The layers wereseparated. The organic layer was dried over magnesium sulfate and thenconcentrated to provide an off-white solid. This material wasrecrystallized from 8:2 ethanol:water to provide a white solid. Aportion of this material was purified by prep HPLC eluting withwater/acetonitrile/trifluoroacetic acid to provide 0.6 g ofN¹-[2-(4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentanamideas the ditrifluoroacetate salt, m.p. 171-175° C. Analysis: Calculatedfor: C₂₅H₃₃N₇O₃S.2 C₂HF₃O₂: %C, 47.09; %H, 4.77; %N, 13.26; Found: %C,47.06; %H, 5.17; %N, 13.31.

EXAMPLE 30N¹-[4-(4-Amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-(5-methyl-2-oxo-4-imidazolinyl)hexaneamide

1-(4-Aminobutyl)-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine (0.13 g, 0.47mmol), D-desthiobiotin (0.10 g, 0.47 mmol) and chloroform (200 mL) werecombined and stirred at ambient temperature until a clear solution wasobtained. 1-[3-(dimethylamino)propyl-3-ethylcarbodiimide hydrochloride(0.094 g, 0.49 mmol) was added and the reaction mixture was maintainedat ambient temperature overnight. The reaction mixture was poured onto asilica gel column. The chloroform was allowed to run off and then thecolumn was eluted with 10% methanol in dichloromethane. The purefractions were combined and concentrated to provideN¹-[4-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-(5-methyl-2-oxo-4-imidazolinyl)hexaneamideas a white solid.

EXAMPLE 31N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-ethoxy-1-naphthamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and2-ethoxy-1-naphthoyl chloride were combined to provideN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-ethoxy-1-naphthamideas a white powder, m.p. 219° C. (decomposition). ¹H NMR (300 MHz,DMSO-d₆) δ8.33 (t, J=5.8 Hz, 1H), 8.22 (s, 1H), 8.09 (d, J=8.0 Hz, 1H),7.91 (d, J=8.7 Hz, 1H), 7.87-7.84 (m, 1H), 7.64-7.56 (m, 2H), 7.47-7.22(m, 5H), 6.60 (s, 2H), 4.69 (t, J=7.2 Hz, 2H), 4.09 (q, J=7.2 Hz, 2H),3.37 (m, 2H), 2.01 (m, 2H), 1.64 (m, 2H), 1.18 (t, J=7.2 Hz, 3H); MS(EI) m/e 453.2157 (453.2165 calcd for C₂₇H₂₇N₅O₂).

EXAMPLE 32N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-cyanobenzamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and 4-cyanobenzoylchloride were combined to provideN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-cyanobenzamide asa white powder, m.p. 222.8-225.3 ° C. ¹H NMR (300 MHz, DMSO-d₆) δ8.73(t, J=5.7 Hz, 1H), 8.22 (s, 1H), 8.03 (d, J=8.1 Hz, 1H), 7.93 (s, 4H),7.61 (dd, J=8.4, 1.2 Hz, 1H), 7.43 (dt, J=7.6, 1.5 Hz, 1H), 7.21 (dt,J=7.6, 1.2 Hz, 1H), 6.61 (s, 2H), 4.64 (t, J=7.2 Hz, 2H), 3.33 (m, 2H),1.96 (quintet, J=7.2 Hz, 2H), 1.58 (quintet, J=7.2 Hz, 2H); IR (KBr)3441, 3337, 3136, 2945, 2228, 1641, 1545, 1531, 1481, 1396, 1309, 1257,857, 755 cm⁻¹; MS (El) m/e 384.1699 (384.1699 calcd for C₂₂H₂₀N₆O).

EXAMPLE 33N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-3-cyanobenzamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and 3-cyanobenzoylchloride were combined to provideN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-3-cyanobenzamide asa white crystalline solid, m.p. 200.0-201.0° C. (decomposition). ¹H NMR(300 MHz, DMSO-d₆) δ8.68 (t, J=5.7 Hz, 1H), 8.22 (s, 1H), 8.17 (t, J=1.8Hz, 1H), 8.10-7.97 (m, 3H), 7.69-7.60 (m, 2H), 7.42 (dt, J=7.5, 1.2 Hz,1H), 7.20 (dt, J=7.5, 1.5 Hz, 1H), 6.62 (s, 2H), 4.63 (t, J=6.9 Hz, 2H),3.32 (m, 2H), 1.91 (quintet, J=7.5 Hz, 2H), 1.59 (quintet, J=7.5 Hz,2H); IR (KBr) 3455, 3295, 3072, 2941, 2231, 1638, 1581, 1527, 1479,1396, 1312, 1251, 1205 cm⁻¹; MS (EI) m/e 384.1699 (384.1699 calcd forC₂₂H₂₀N₆O).

EXAMPLE 34N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-phenylbenzamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and4-biphenylcarbonyl chloride were combined to provideN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-phenylbenzamideas a white powder, m.p. 215.4° C. (decomposition). ¹H NMR (300 MHz,DMSO-d₆) δ8.54 (t, J=5.7 Hz, 1H), 8.22 (s, 1H), 8.05 (d, J=7.2 Hz, 1H),7.88 (d, J=5.4 Hz, 2H), 7.75-7.70 (m, 4H), 7.62 (dd, J=8.4, 1.5 Hz, 1H),7.52-7.38 (m, 4H), 7.22 (dt, J=7.5, 1.2 Hz, 1H), 6.61 (s, 2H), 4.65 (t,J=7.2 Hz, 2H), 3.30 (m, 2H), 1.93 (quintet, J=7.5 Hz, 2H), 1.60(quintet, J=7.5 Hz, 2H); MS (EI) m/e 435.2054 (435.2059 calcd forC₂₇H₂₅N₅O).

EXAMPLE 35N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-phenoxyacetamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and phenoxyacetylchloride were combined to provideN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-phenoxyacetamideas an off white powder, m.p. 61.5° C. (decomposition). ¹H NMR (300 MHz,DMSO-d₆) δ8.19 (s, 1H), 8.12 (t, J=6.0 Hz, 1H), 8.03 (d, J=8.4 Hz, 1H),7.62 (dd, J=8.4, 1.2 Hz, 1H), 7.44 (dt, J=7.5, 1.2 Hz, 1H), 7.29-7.21(m, 3H), 6.96-6.88 (m, 3H), 6.62 (s, 2H), 4.60 (t, J=7.2 Hz, 2H), 4.42(s, 2H), 3.16 (q, J=6.9 Hz, 2H), 1.83 (quintet, J=7.2 Hz, 2H), 1.47(quintet, J=7.2 Hz, 2H); IR (KBr) 3311, 3180, 2937, 1664, 1618, 1583,1527, 1493, 1480, 1396, 1244, 755 cm⁻¹; MS (EI) m/e 389.1844 (389.1852calcd for C₂₂H₂₃N₅O₂).

EXAMPLE 36N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-ethylhexanamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and 2-ethylhexanoylchloride were combined to provideN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-ethylhexanamideas a tan powder, m.p. 163.0-164.0° C. ¹H NMR (300 MHz, DMSO-d₆) δ8.19(s, 1H), 8.03 (d, J=8.1 Hz, 1H), 7.79 (m, 1H), 7.61 (dd, J=8.1, 1.2 Hz1H), 7.44 (dt, J=7.5, 1.2 Hz, 1H), 7.26 (dt, J=7.5, 1.2 Hz, 1H), 6.63(s, 2H), 4.61 (t, J=6.9 Hz, 2H), 3.12-3.05 (m, 2H), 1.94-1.82 (m, 3H),1.49-1.03 (m, 10H), 0.76 (t, J=7.2 Hz, 3H), 0.67 (t, J=7.2 Hz, 3H), MS(EI) m/e 381.2533 (381.2529 calcd for C₂₂H₃₁N₅O).

EXAMPLE 37N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-(trans)-2-phenylcyclopropane-1-carboxamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine andtrans-2-phenyl-1-cyclopropanecarbonyl chloride were combined to provideN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-(trans)-2-phenylcyclopropane-1-carboxamideas an off white solid, m.p. 77.0° C. ¹H NMR (300 MHz, DMSO-d₆) δ7.90(dd, J=8.1, 1.2 Hz, 1H), 7.81 (dd, J=8.1, 1.2 Hz, 1H), 7.78 (s, 1H),7.50 (dt, J=8.1, 1.5 Hz, 1H), 7.33-7.15 (m, 4H), 7.05-7.02 (m, 2H), 5.84(broad s, 1H), 5.51 (s, 2H), 4.52 (t, J=7.2 Hz, 2H), 3.32 (q, J=6.6 Hz,2H), 2.49-2.43 (m, 1H), 2.07-1.95 (m, 3H), 1.64-1.51 (m, 3H), 1.25-1.18(m, 1H); IR (KBr) 3304, 3179, 2939, 1640, 1582, 1527, 1479, 1396, 1250,755, 735, 689 cm⁻¹; MS (EI) m/e 399.2059 (399.2059 calcd for C₂₄H₂₅N₅O).

EXAMPLE 38N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-1-naphthamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and 1-naphthoylchloride were combined to provideN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-1-naphthamide as anoff white powder, m.p. 174.5° C. (decomposition). ¹H NMR (300 MHz,DMSO-d₆) δ8.52 (t, J=5.6 Hz, 1H), 8.49 (s, 1H), 8.24 (m, 3H), 8.10 (d,J=8.1 Hz, 1H), 7.97 (m, 2H), 7.80 (d, J=8.2 Hz, 1H), 7.65 (t, J=7.3 Hz,1H), 7.57-7.41 (m, 5H), 4.75 (t, J=6.9 Hz, 2H), 2.03-1.98 (m, 2H),1.69-1.64 (m, 2H); MS (EI) m/e 409.1903 (409.1903 calcd for C₂₅H₂₃N₅O).

EXAMPLE 39N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-3-phenoxybenzamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and 3-phenoxybenzoylchloride were combined to provideN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-3-phenoxybenzamideas a white powder, m.p. 105.0-107.0° C. ¹H NMR (300 MHz, DMSO-d₆) δ8.54(t, J=5.4 Hz, 1H), 8.34 (s, 1H), 8.10 (d, J=8.1 Hz, 1H), 7.69 (dd,J=8.1, 1.2 Hz, 1H), 7.58-7.29 (m, 9H), 7.19-7.13 (m, 2H), 7.04-6.99 (m,2H), 4.65 (t, J=7.2 Hz, 2H), 3.28 (m, 2H), 1.89 (quintet, J=7.2 Hz, 2H),1.58 (quintet, J=7.2 Hz, 2H); MS (EI) m/e 451.2012 (451.2008 calcd forC₂₇H₂₅N₅O₂).

EXAMPLE 40N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-3-quinolinecarboxamide

According to the general method of Example 14,1-(4-arninobutyl)-1H-imidazo[4,5-c]quinolin-4-amine andquinoline-3-carbonyl chloride were combined to provideN³-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-3-quinolinecarboxamideas a white crystalline solid, m.p. 116.0-118.0° C. (decomposition). ¹HNMR (300 MHz, DMSO-d₆) δ9.24 (d, J=2.1 Hz, 1H), 8.86 (t, J=5.1 Hz, 1H),8.74 (d, J=2.1 Hz, 1H), 8.25 (s, 1H), 8.09-8.05 (m, 3H), 7.86 (dt,J=7.5, 1.0 Hz, 1H), 7.69 (t, J=7.5 Hz, 1H), 7.61 (d, J=7.5 Hz, 1H), 7.40(t, J=7.5 Hz, 1H), 7.21 (t, J=7.5 Hz, 1H), 6.68 (s, 2H), 4.67 (t, J=6.9Hz, 2H), 1.97 (quintet, J=7.2 Hz, 2H), 1.65 (quintet, J=7.2 Hz, 2H); MS(EI) m/e 410.1864 (410.1855 calcd for C₂₄H₂₂N₆O).

EXAMPLE 41 N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-phenoxypropanamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and2-phenoxypropionyl chloride were combined to provideN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-phenoxypropanamideas a white powder, m.p. 85.0-87.5° C. ¹H NMR (300 MHz, DMSO-d₆) δ8.15(s, 1H), 8.07 (t, J=6.0 Hz, 1H), 8.00 (d, J=8.4 Hz, 1H), 7.62 (dd,J=8.4, 1.2 Hz, 1H), 7.43 (dt, J=7.5, 1.2 Hz, 1H), 7.28-7.16 (m, 3H),6.91-6.81 (m, 3H), 6.57 (s, 2H), 4.62-4.53 (m, 3H), 3.10 (q, J=6.9 Hz,2H), 1.76 (quintet, J=7.1 Hz, 2H), 1.43 (quintet, J=7.1 Hz, 2H), 1.33(d, J=6.6 Hz, 3H); MS (EI) m/e 403.2005 (403.2008 calcd for C₂₃H₂₅N₅O₂).

EXAMPLE 42N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-1-benzyl-1H-3-indolecarboxamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and1-benzylindole-3-carbonyl chloride were combined to provideN³-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-1-benzyl-1H-3-indolecarboxamideas a white powder, m.p. 139.0° C. (decomposition). ¹H NMR (300 MHz,DMSO-d₆) δ8.24 (s, 1H), 8.14 (t, J=7.8 Hz, 1H), 8.04 (m, 2H), 7.93 (m,1H), 7.62 (d, J=8.4 Hz, 1H), 7.51 (d, J=7.8 Hz, 1H), 7.44-7.09 (m, 9H),6.63 (s, 2H), 5.44 (s, 2H), 4.66 (t, J=6.6 Hz, 2H), 1.97-1.92 (m, 2H),1.62-1.57 (m, 2H); MS (EI) m/e 488.2326 (488.2325 calcd for C₃₀H₂₈N₆O).

EXAMPLE 43N²-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-naphthamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and 2-naphthoylchloride were combined to provideN²-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-naphthamide as awhite powder, m.p. 257.0° C. (decomposition). ¹H NMR (300 MHz, DMSO-d₆)δ8.85 (broad s, 2H), 8.69 (broad s, 1H), 8.57 (s, 1H), 8.38 (s, 1H),8.25 (d, J=8.4 Hz, 1H), 7.99-7.80 (m, 5H), 7.75-7.50 (m, 4H), 4.75 (t,J=6.9 Hz, 2H), 3.39 (m, 2H), 1.98 (quintet, J=7.2 Hz, 2H), 1.68(quintet, J=7.2 Hz, 2H); MS (EI) m/e 409.1909 (409.1903 calcd forC₂₅H₂₃N₅O).

EXAMPLE 44N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2,6-dimethoxynicotinamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and2,6-dimethoxynicotinoyl chloride were combined to provideN³-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2,6-dimethoxynicotinamideas an off white powder, m.p. 175.0-177.0° C. ¹H NMR (300 MHz, DMSO-d₆)8.21 (s, 1H), 8.11-8.02 (m, 3H), 7.62 (d, J=8.2 Hz, 1H), 7.42 (t, J=7.5Hz, 1H), 7.20 (t, J=7.5 Hz, 1H), 6.58 (broad s, 2H), 6.46 (d, J=8.3 Hz,1H), 4.63 (t, J=7.0 Hz, 2H), 3.90 (s, 3H), 3.88 (s, 3H), 3.30 (m, 2H),1.90 (m, 2H), 1.57 (m, 2H); MS (EI) m/e 420.1909 (420.1910 calcd forC₂₂H₂₄N₆O₃).

EXAMPLE 45N⁸-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-8-quinolinecarboxamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine andquinoline-8-carbonyl chloride were combined to provideN⁸-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-8-quinolinecarboxamideas a tan powder, m.p. 91.0-93.0° C. ¹H NMR (300 MHz, DMSO-d₆) δ10.80 (t,J=5.5 Hz, 1H), 8.79 (dd, J=4.3, 1.8 Hz, 1H), 8.55-8.49 (m, 2H), 8.24 (s,1H), 8.17 (dd, J=8.1, 1.5 Hz, 1H), 8.06 (d, J=7.2 Hz, 1H), 7.73 (t,J=7.8 Hz, 1H), 7.63-7.59 (m, 2H), 7.40 (dt J=7.1, 1.2 Hz, 1H), 7.14 (dt,J=7.1, 1.2 Hz, 1H), 6.57 (broad s, 2H), 4.68 (t, J=7.0 Hz, 2H), 3.51 (m,2H), 2.02 (m, 2H), 1.69 (m, 2H); MS (EI) m/e 410.1858 (410.1855 calcdfor C₂₄H₂₂N₆O).

EXAMPLE 46N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-(4-isobutylphenyl)propanamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and4-isobutyl-α-methylphenylacetyl chloride were combined to provideN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-(4-isobutylphenyl)propanamideas a white powder, m.p. 172.0-173.0° C. ¹H NMR (300 MHz, DMSO-d₆) δ8.14(s, 1H), 8.01 (d, J=7.6 Hz, 1H), 7.90 (t, J=5.6 Hz, 1H), 7.63 (dd,J=8.1, 1.0 Hz, 1H), 7.44 (dt, J=7.0, 1.0 Hz, 1H), 7.25 (dt, J=7.0 Hz,1H), 7.14 (d, J=8.0 Hz, 2H), 6.97 (d, J=8.0 Hz, 2H), 6.58 (broad s, 2H),4.55 (t, J=7.0 Hz, 2H), 3.47 (q, J=7.1 Hz, 1H), 3.06 (m, 2H), 2.34 (d,J=7.1 Hz, 2H), 1.80-1.69 (m, 3H), 1.44 (m, 2H), 1.24 (d, J=7.0 Hz, 3H),0.82 (d, J=6.6 Hz,6H); MS (EI) m/e 443.2687 (443.2685 calcd forC₂₇H₃₃N₅O).

EXAMPLE 47N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]nicotinamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and nicotinoylchloride hydrochloride were combined to provideN³-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]nicotinamide as awhite powder, m.p. 188.6-189.5° C. ¹H NMR (300 MHz, DMSO-d₆) δ8.95 (dd,J=2.2, 0.7 Hz, 1H), 8.70-8.65 (m, 2H), 8.22 (s, 1H), 8.11 (dt, J=8.3,2.0 Hz, 1H), 8.04 (dd, J=8.2, 0.9 Hz, 1H), 7.61 (dd, J=8.3, 1.1 Hz, 1H),7.50-7.39 (m, 2H), 7.23-7.18 (m, 1H), 6.58 (broad s, 2H), 4.64 (t, J=7.0Hz, 2H), 3.30 (m, 2H), 1.93 (m, 2H), 1.60 (m, 2H); MS (EI) m/e 360.1696(360.1699 calcd for C₂₀H₂₀N₆O).

EXAMPLE 48N⁴-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]isonicotinamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and isonicotinoylchloride hydrochloride were combined to provideN⁴-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]isonicotinamide as awhite crystalline solid, m.p. 213.0-213.7° C. ¹H NMR (300 MHz, DMSO-d₆)δ8.76 (m, 1H), 8.69 (d, J=5.6 Hz, 2H), 8.22 (s, 1H), 8.04 (d, J=8.0 Hz,1H), 7.67 (d, J=5.7 Hz, 2H), 7.62 (d, J=8.2 Hz, 1H), 7.43 (t, J=7.5 Hz,1H), 7.21 (t, J=7.5 Hz, 1H), 6.62 (broad s, 2H), 4.64 (t, J=6.8 Hz, 2H),3.30 (m, 2H), 1.92 (m, 2H), 1.58 (m, 2H); MS (EI) m/e 360.1699 (360.1699calcd for C₂₀H₂₀N₆O).

EXAMPLE 49N⁴-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-quinolinecarboxamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine andquinoline-4-carbonyl chloride were combined to provideN⁴-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-quinolinecarboxamideas a white crystalline solid, m.p. 214.5-215.2° C. ¹H NMR (300 MHz,DMSO-d₆) δ8.89 (d, J=4.3 Hz, 1H), 8.76 (t, J=5.6 Hz, 1H), 8.24 (s, 1H),8.10-8.01 (m, 3H), 7.78 (ddd, J=8.4, 6.9, 1.5 Hz, 1H), 7.64 (dd, J=8.4,1.1 Hz, 1H), 7.56 (ddd, J=8.3, 6.9, 1.4 Hz, 1H), 7.44 (ddd, J=8.3, 7.0,1.3 Hz, 1H), 7.34 (d, J=4.3 Hz, 1H), 7.24 (ddd, J=8.3, 7.0, 1.3 Hz, 1H),6.60 (broad s, 2H), 4.68 (t, J=6.9 Hz, 2H), 3.38 (q, J=7.0 Hz, 2H), 2.00(m, 2H), 1.63 (m, 2H); MS (EI) m/e 410.1860 (410.1855 calcd forC₂₄H₂₂N₆O).

EXAMPLE 50N⁴-[4-(4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-phenyl-4-quinolinecarboxamide

1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.57 g,3.0 mmol) was added dropwise to a chilled (0° C.) solution of2-phenyl-4-quinolinecarboxylic acid (0.5 g, 3.7 mmol),1-hydroxybenzotriazole (0.5 g, 3.7 mmol), pyridine (2.2 ml), anddichloromethane (20 ml). The reaction was maintained for 15 min followedby the dropwise addition of1-(4-aminobutyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amine(0.8 g, 2.55 mmol) in dichloromethane (100 ml). The reaction wasmaintained at room temperature overnight. The solvent was removed invacuo and the residue was purified by flash column chromatography(silica gel, 9:1 dichloromethanemethanol). The fractions containingproduct were combined, washed with saturated aqueous sodium bicarbonate,dried (MgSO₄), filtered, and concentrated to provide 0.62 g ofN⁴-[4-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-phenyl-4-quinolinecarboxamideas a yellow crystalline solid, m.p. 118° C. (decomposition). ¹H NMR (300MHz, DMSO-d₆) δ8.88 (t, J=5.7 Hz, 1H), 8.24-8.21 (m, 2H), 8.13-8.01(m,4H), 7.83-7.78 (m, 1H), 7.62-7.48 (m, 5H), 7.36 (m, 1H), 7.20 (dt,J=7.6, 1.2 Hz, 1H), 6.54 (broad s, 2H), 4.62 (t, J=7.2 Hz, 2H), 3.83 (t,J=6.7 Hz, 2H), 3.45 (m, 2H), 3.29-3.20 (m, 5H), 1.96 (m, 2H), 1.79 (m,2H); MS (EI) m/e 544.2589 (544.2587 calcd for C₃₃H₃₂N₆O₂)

EXAMPLE 51N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-(pentylsulfanyl)nicotinamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and2-(n-pentylthio)pyridine-3-carbonyl chloride were combined to provideN³-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-(pentylsulfanyl)nicotinamideas a tan powder, m.p. 158.0-161.0° C. ¹H NMR (300 MHz, DMSO-d₆)δ8.47-8.41 (m, 2H), 8.21 (s, 1H), 8.06 (d, J=8.2 Hz, 1H), 7.63 (dd,J=8.3, 1.1 Hz, 1H), 7.54 (dd, J=7.6, 1.8 Hz, 1H), 7.47-7.41 (m, 1H),7.26-7.21 (m, 1H), 7.08 (dd, J=7.5, 4.8 Hz, 1H), 6.57 (broad s, 2H),4.64 (t, J=6.9 Hz, 2H), 3.27 (m, 2H), 2.98 (t, J=7.3 Hz, 2H), 1.96 (m,2H), 1.62-1.46 (m, 4H), 1.35-1.20 (m, 4H), 0.83 (t, J=7.1 Hz, 3H); MS(EI) m/e 462.2196 (462.2202 calcd for C₂₅H₃oN₆OS).

EXAMPLE 52N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-cyanonicotinamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and6-cyanopyridine-3-carbonyl chloride were combined to provideN³-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-cyanonicotinamideas an off white powder, m.p. 125.0-129.0° C. ¹H NMR (300 MHz, DMSO-d₆)δ9.05 (dd, J=2.1, 0.8 Hz, 1H), 8.88 (t, J=5.6 Hz, 1H), 8.31 (dd, J=8.1,2.1 Hz, 1H), 8.21 (s, 1H), 8.14 (dd, J=8.1, 0.8 Hz, 1H), 8.03 (m, 1H),7.62 (dd, J=8.3, 1.1 Hz, 1H), 7.42 (m, 1H), 7.20 (m, 1H), 6.59 (broad s,2H), 4.64 (t, J=6.9 Hz, 2H), 3.30 (m, 2H), 1.93 (m, 2H), 1.59 (m, 2H);MS (EI) m/e 385.1648 (385.1651 calcd for C₂₁H₁₉N₇O).

EXAMPLE 53N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-chloronicotinamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and6-chloropyridine-3-carbonyl chloride were combined to provideN³-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-chloronicotinamideas an off white crystalline solid, m.p. 144.0-148.0° C. (decomposition).¹H NMR (300 MHz, DMSO-d₆) δ8.77 (dd, J=2.5, 0.6 Hz, 1H), 8.73 (t, J=5.6Hz, 1H), 8.22 (s, 1H), 8.16 (dd, J=8.3, 2.5 Hz, 1H), 8.03 (m, 1H), 7.63(d, J=0.5 Hz, 1H), 7.60 (d, J=0.5 Hz, 1H), 7.45-7.40 (m, 1H), 7.23-7.18(m, 1H), 6.61 (broad s, 2H), 4.63 (t, J=6.9 Hz, 2H), 3.30 (m, 2H), 1.92(m, 2H), 1.58 (m, 2H). MS (EI) m/e 394.1298 (394.1309 calcd forC₂₀Hl₉N₆OCl).

EXAMPLE 54N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-(2,2,2-trifluoroethoxy)nicotinamide

According to the general method of Example 14,1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and6-(2,2,2-trifluoroethoxy)pyridine-3-carbonyl chloride were combined toprovideN³-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-(2,2,2-trifluoroethoxy)nicotinamideas a white crystalline solid, m.p. 192.0-194.0° C. (decomposition). ¹HNMR (300 MHz, DMSO-d₆) δ8.62 (d, J=1.9 Hz, 1H), 8.58 (t, J=5.6 Hz, 1H),8.25 (s, 1H), 8.15 (dd, J=8.6, 2.4 Hz, 1H), 8.06 (d, J=7.6 Hz, 1H), 7.64(d, J=7.8 Hz, 1H), 7.45 (t, J=7.1 Hz, 1H), 7.24 (t, J=7.1 Hz, 1H), 7.04(d, J=8.6 Hz, 1H), 6.82 (broad s, 2H), 5.06 (q, J=9.1 Hz, 2H), 4.64 (t,J=6.9 Hz, 2H), 3.30 (m, 2H), 1.91 (m, 2H), 1.60 (m, 2H); MS (EI) m/e458.1678 (458.1678 calcd for C₂₂H₂₁N₆O₂F₃).

EXAMPLE 55N²-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-2-quinolinecarboxamide

According to the general method of Example 14,1-(4-aminobutyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amineand quinoline-2-carbonyl chloride were combined in dichloromethane andtriethylamine (3 equivalents) to provideN²-{4-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-2-quinolinecarboxamideas a white solid, m.p. 78.1-79.9° C. ¹H NMR (300 MHz, DMSO-d₆) δ9.02 (t,J=6.1 Hz, 1H), 8.55 (d, J=8.5 Hz, 1H), 8.23 (d, J=8.5 Hz, 1H), 8.10 (t,J=7.6 Hz, 1H), 8.02 (d, J=7.6 Hz, 1H), 7.90-7.84 (m, 1H), 7.75-7.70 (m,1H), 7.58 (dd, J=8.3, 1.0 Hz, 1H), 7.35-7.30 (m, 1H), 7.18-7.13 (m, 2H),6.48 (broad s, 2H), 4.58 (m, 2H), 3.79 (t, J=6.7 Hz, 2H), 3.44 (m, 2H),3.22 (m, 5H), 1.91-1.78 (m, 4H); MS (EI) m/e 468.2276 (468.2274 calcdfor C₂₇H₂₈N₆O₂).

EXAMPLE 56N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-(2-fluoro-4-biphenylyl)propanamide

According to the general method of Example 14,1-(4-aminobutyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amineand 2-(2-fluoro-4-biphenylyl)propionyl chloride were combined to provideN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-(2-fluoro-4-biphenylyl)propanamideas a white powder, m.p. 76.1-79.9° C. ¹H NMR (300 MHz, DMSO-d₆) δ8.17(s, 1H), 8.03 (m, 2H), 7.62 (d, J=8.3 Hz, 1H), 7.49-7.14 (m, 10H), 6.59(broad s, 2H), 4.58 (t, J=6.9 Hz, 2H), 3.59 (q, J=7.0 Hz, 1H), 3.09(pentet, J=6.7 Hz, 2H), 1.82 (m, 2H), 1.45 (m, 2H), 1.30 (d, J=7.0 Hz,3H); MS (EI) m/e 481.2268 (481.2278 calcd for C₂₉H₂₈FN₅O).

EXAMPLE 57N¹-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-1-isoquinolinecarboxamide

According to the general method of Example 50,1-(4-aminobutyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amineand isoquinoline-1-carboxylic acid were combined to provideN¹-{4-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-1-isoquinolinecarboxamideas a yellow crystalline solid, m.p. 61.0-63.0° C. ¹H NMR (300 MHz,DMSO-d₆) δ8.94 (t, J=5.9 Hz, 1H), 8.87 (d, J=8.5 Hz, 1H), 8.51 (d, J=5.6Hz, 1H), 8.05-7.96 (m, 3H), 7.84-7.96 (m, 1H), 7.70-7.65 (m, 1H), 7.61(dd, J=8.3, 1.1 Hz, 1H), 7.37 (dt, J=7.7, 1.0 Hz, 1H), 7.19 (dt, J=7.6,1.2 Hz, 1H), 6.53 (broad s, 2H), 4.60 (t, J=7.2 Hz, 2H), 3.81 (t, J=6.7Hz, 2H), 3.41 (m, 2H), 3.28-3.12 (m, 5H), 1.92-1.76 (m, 4H); MS (EI) m/e468.2261 (468.2274 calcd for C₂₇H₂₈N₆O₂).

EXAMPLE 58N²-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-5-butyl-2-pyridinecarboxamide

According to the general method of Example 50,1-(4-aminobutyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amineand fusaric acid were combined to provideN²-{4-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-5-butyl-2-pyridinecarboxamideas a tan solid, m.p. 54.9-55.2° C. ¹H NMR (300 MHz, DMSO-d₆) δ8.81 (t,J=6.1 Hz, 1H), 8.44 (m, 1H), 7.98 (d, J=7.3 Hz, 1H), 7.94 (dd, J=8.0,0.7 Hz, 1H), 7.80 (dd, J=8.0, 2.2 Hz, 1H), 7.60 (dd, J=8.3, 1.2 Hz, 1H),7.39-7.34 (m, 1H), 7.16-7.10 (m, 1H), 6.52 (broad s, 2H), 4.55 (t, J=6.9Hz, 2H), 3.79 (t, J=6.7 Hz, 2H), 3.23 (s, 3H), 3.18 (t, J=6.7 Hz, 2H),2.67 (t, J=7.6 Hz, 2H), 1.83-1.72 (m, 4H), 1.63-1.53 (m, 2H), 1.34-1.24(m, 2H), 0.90 (t, J=7.3 Hz, 3H); MS (EI) m/e 474.2750 (474.2743 calcdfor C₂₇H₃₄N₆O₂).

EXAMPLE 59N³-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-3-indolecarboxamide

According to the general method of Example 50,1-(4-aminobutyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amineand indole-3-carboxylic acid were combined to provideN³-{4-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-3-indolecarboxamideas a white powder, m.p. 225.5-227.4° C. ¹H NMR (300 MHz, DMSO-d₆) δ11.50(broad s, 1H), 8.13 (d, J=7.9 Hz, 1H), 8.06 (d, J=10.2 Hz, 1H),7.95-7.89 (m, 2H), 7.61 (d, J=8.3 Hz, 1H), 7.43-7.35 (m, 2H), 7.20-7.05(m, 3H), 6.48 (broad s, 2H), 4.58 (t, J=7.2 Hz, 2H), 3.80 (t, J=6.6 Hz,2H), 3.33 (m, 2H), 3.24-3.18 (m, 5H), 1.88 (m, 2H), 1.70 (m, 2H); ¹³CNMR (75 MHz, DMSO-d₆) δ165.0, 152.0, 151.0, 145.1, 136.4, 132.6, 127.8,126.8, 126.6, 126.4, 122.1, 121.5, 121.4, 120.6, 120.3, 115.1, 112.1,111.0, 70.5, 58.4, 45.1, 38.2, 27.7, 27.5, 27.0; MS (EI) m/e 456.2282(456.2274 calcd for C₂₆H₂₈N₆O₂).

EXAMPLE 60N¹-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-4-(1-pyrrolyl)benzamide

According to the general method of Example 50,1-(4-aminobutyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amineand 4-(1-pyrrolyl)benzoic acid were combined to provideN¹-{4-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-4-(1-pyrrolyl)benzamideas an off white powder, m.p. 173.0-174.9° C. ¹H NMR (300 MHz, DMSO-d₆)δ8.52 (t, J=5.5 Hz, 1H), 8.02 (d, J=7.9 Hz, 1H), 7.90 (d, J=8.7 Hz, 2H),7.67 (d, J=8.7 Hz, 2H), 7.61 (dd, J=8.4, 1.1 Hz, 1H), 7.48 (t, J=2.2 Hz,2H), 7.39 (m, 1H), 7.19 (dt, J=7.6, 1.1 Hz, 1H), 6.53 (broad s, 2H),6.30 (t, J=2.2 Hz, 2H), 4.57 (t, J=7.0 Hz, 2H), 3.82 (t, J=6.7 Hz, 2H),3.33 (m, 2H), 3.26 (s, 3H), 3.20 (t, J=6.7 Hz, 2H), 1.87 (m, 2H), 1.71(m, 2H); MS (EI) m/e 482.2421 (482.2430 calcd for C₂₈H₃₀N₆O₂).

EXAMPLE 61N²-{4-[4-Amino-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-2-quinolinecarboxamide

Quinoline-2-carbonyl chloride (0.28 g in 10 ml dichloromethane, 1.46nmmol) was added dropwise to a stirring solution of1-(4-aminobutyl)-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-4-amine(0.49 g, 1.3 mmol), dichloromethane (140 ml) and triethylamine (0.5 ml).The reaction was maintained for 17 hours and then concentrated in vacuo.The yellow residue was partitioned between dichloromethane and saturatedaqueous sodium bicarbonate. The organic fraction was dried (MgSO₄),filtered, and concentrated. The crude residue was purified by flashcolumn chromatography (silica gel, gradient elution usingdichloromethane to 95:5 dichloromethanemethanol) to provide 0.19 g ofN²-{4-[4-amino-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-2-quinolinecarboxamideas an off white solid, m.p. 95.1-97.4° C. ¹H NMR (300 MHz, DMSO-d₆)δ8.97 (t, J=6.0 Hz, 1H), 8.56 (d, J=8.4 Hz, 1H), 8.16-8.07 (m, 3H), 7.96(d, J=7.7 Hz, 1H), 7.87 (m, 1H), 7.72 (m, 1H), 7.58 (dd, J=8.3, 1.1 Hz,1H), 7.31 (m, 1H), 7.23 (d, J=8.7 Hz, 2H), 7.08 (m, 1H), 6.82 (d, J=8.7Hz, 2H), 6.58 (broad s, 2H), 4.50 (m, 2H), 4.33 (s, 2H), 3.63 (s, 3H),3.34 (m, 2H), 1.65 (m, 4H); MS (EI) m/e 530.2431 (530.2430 calcd forC₃₂H₃₀N₆O₂).

EXAMPLE 62N³-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-6-(1-pyrrolyl)nicotinamide

According to the general method of Example 50,1-(4-aminobutyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amineand 2-pyrrolopyridine-5-carboxylic acid were combined to provideN³{4-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-6-(1-pyrcolyl)nicotinamideas a yellow crystalline solid, m.p. 77.0-80.0° C. ¹H NMR (300 MHz,CDCl₃) 8.72 (d, J=2.3 Hz, 1H), 8.07 (dd, J=8.4, 2.4 Hz 1H), 7.92 (d,J=7.3 Hz, 1H), 7.82 (d, J=7.4 Hz, 1H), 7.55 (t, J=2.2 Hz, 2H), 7.49 (m,1H), 7.37 (m, 2H), 6.39 (d, J=2.2 Hz, 2H), 6.20 (m, 1H), 5.42 (broad s,2H), 4.59 (t, J=7.5 Hz, 2H), 3.90 (t, J=7.4 Hz, 2H), 3.56 (q, J=6.7 Hz,2H), 3.36 (s, 3H), 3.20 (t, J=6.4 Hz, 2H), 2.05 (m, 2H), 1.82 (m, 2H);MS (EI) m/e 483.2376 (483.2383 calcd for C₂₇H₂₉N₇O₂).

EXAMPLE 63N⁵-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-5-indolecarboxamide

According to the general method of Example 50,1-(4-aminobutyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amineand indole-5-carboxylic acid were combined to provideN⁵-{4-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-5-indolecarboxamideas an off white solid. ¹H NMR (300 MHz, DMSO-d₆) δ11.31 (s, 1H), 8.34(t, J=5.5 Hz, 1H), 8.06 (m, 2H), 7.63-7.58 (m, 2H), 7.42-7.38 (m, 3H),7.22 (t, J=7.1 Hz, 1H), 6.67 (broad s, 2H), 6.50 (s, 1H), 4.58 (m, 2H),3.81 (t, J=6.6 Hz, 2H), 3.34 (m, 2H), 3.25 (s, 3H), 3.21 (t, J=6.6 Hz,2H), 1.89 (m, 2H), 1.72 (m,2H); MS (EI) m/e 456.2264 (456.2274 calcd forC₂₆H₂₈N₆O₂).

EXAMPLE 64N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-phenoxybenzamide

According to the general method of Example 14,1-(4-arninobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and 4-phenoxybenzoylchloride were combined to provideN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-phenoxybenzamideas a white powder, m.p. 90.5-91.5° C. ¹H NMR (500 MHz, DMSO-d₆) δ8.42(t, J=5.7 Hz, 1H), 8.21 (s, 1H), 8.03 (d, J=7.9 Hz, 1H), 7.81 (d, J=8.9Hz, 2H), 7.62 (d, J=7.9 Hz, 1H), 7.45-7.40 (m, 3H), 7.21 (m, 2H), 7.07(d, J=7.6 Hz, 2H), 6.99 (d, J=8.9 Hz, 2H), 6.61 (broad s, 2H), 4.63 (t,J=7.0 Hz, 2H), 3.25 (m, 2H), 1.92 (m, 2H), 1.58 (m, 2H); MS (EI) m/e451.2008 (451.2008 calcd for C₂₇H₂₅N₅O₂).

EXAMPLE 65N⁵-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-5-(2-phenyl-1-ethynyl)nicotinamide

According to the general method of Example 50,1-(4-aminobutyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amineand 5-(phenylethynyl)pyridine-3-carboxylic acid were combined to provideN⁵-{4-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-5-(2-phenyl-1-ethynyl)nicotinamideas a yellow solid, m.p. 76.0-78.0° C. ¹H NMR (300 MHz, DMSO-d6) δ8.95(d, J=2.1 Hz, 1H), 8.87 (d, J=2.0 Hz, 1H), 8.79 (t, J=2.1 Hz, 1H), 8.31(d, J=2.0 Hz, 1H), 8.02 (d, J=8.1 Hz, 1H), 7.61 (m, 3H), 7.48 (m, 3H),7.40 (m, 1H), 7.19 (m, 1H), 6.56 (broad s, 2H), 4.57 (t, J=7.4 Hz, 2H),3.82 (t, J=6.7 Hz, 2H), 3.37 (m, 2H), 3.27 (s, 3H), 3.21 (t, J=6.7 Hz,2H), 1.89 (m, 2H), 1.72 (m, 2H); MS (CI) m/e 519 (M+H).

EXAMPLE 66N³-[4-(4-Amino-2-phenyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]nicotinamide

Part A

A solution of benzoyl chloride (5.3 g, 37.7 mmol) in dichloromethane(100 mL) was slowly added to a solution of tert-butylN-{4-[(3-aminoquinolin-4-yl)amino]butyl}carbamate (12.5 g, 37.7 mmol) indichloromethane (250 mL) at ambient temperature. The reaction mixturewas maintained at ambient temperature overnight. The resultingprecipitate was isolated by filtration and dried to provide 11.0 g oftert-butyl N-(4-{[3-(benzoylamino)quinolin-4-yl]amino}butyl)carbamatehydrochloride as a white solid.

Part B

Triethylamine (7.26 g, 71.7 mmol) was added to a solution of thematerial from Part A in ethanol (200 mL) and heated at reflux for 2days. The reaction mixture was concentrated to provide an orange syrup.HPLC mass spec analysis showed that the syrup contained the desiredproduct and starting material. The syrup was taken up in dichloromethane(100 mL) and then cooled in an ice bath. Triethylamine (5 mL) andbenzoyl chloride (1.9 mL) were added. The reaction mixture wasmaintained at ambient temperature for 2 days at which time analysis byHPLC indicated that the reaction was not complete. The reaction mixturewas concentrated under vacuum. The residue was taken up in isopropylalcohol (150 mL). Triethylamine (5 mL) was added and the reactionmixture was heated at reflux overnight. The reaction mixture wasconcentrated under vacuum. The residue was purified by flashchromatography (silica gel; eluting with 10% methanol indichloromethane). The fractions containing product were combined andconcentrated under vacuum. The residue was recrystallized fromacetonitrile to provide 6.7 g of tert-butylN-[4-(2-phenyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]carbamate as asolid, m.p. 158-159° C.

Part C

3-Chloroperoxybenzoic acid (1.05 eq of 65%) was slowly added in smallportions to a solution of tert-butylN-[4-(2-phenyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]carbamate (6.56 g,15.75 mmol) in dichloromethane (120 mL). After 3 hours the reaction wasquenched with 1% aqueous sodium bicarbonate (200 mL). The layers wereseparated. The aqueous layer was extracted with dichloromethane (2×50mL). The organic fractions were combined, dried over magnesium sulfateand then concentrated under vacuum to provide a pale orange syrup. Thesyrup was triturated with diethyl ether to provide 6.8 g of1-[4-(tert-butylcarbamyl)butyl]-2-phenyl-1H-imidazo[4,5-c]quinoline-5N-oxideas a pale tan solid, m.p. 178-181° C.

Part D

A solution of1-[4-(tert-butylcarbamyl)butyl]-2-phenyl-1H-imidazo[4,5-c]quinoline-5N-oxide(6.8 g, 15.75 mmol) in dichloromethane (100 mL) was chilled in an icebath. Concentrated ammonium hydroxide (30 mL) was added. Tosyl chloride(3.0 g, 15.75 mmol) was added in small portions over a period of 30minutes. The reaction mixture was allowed to warm to ambient temperatureovernight. The reaction was quenched with water (350 mL). The layerswere separated. The aqueous layer was extracted with dichloromethane.The organic fractions were combined, dried over magnesium sulfate andthen concentrated under vacuum to provide a tan solid. This material waspurified by flash chromatography (silica gel eluting with 10% methanolin dichloromethane) to provide 4.8 g of product. The bulk of thematerial was carried on to the next step. A small portion wasrecrystallized from toluene to provide tert-butylN-[4-(4-amino-2-phenyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]carbamate asa solid, m.p. 182-183° C. Analysis: Calculated for C₂₅H₂₉N₅O₂: %C,69.58; %H, 6.77; %N, 16.22; Found: %C, 69.86; %H, 6.95; %N, 15.80.

Part E

The material from Part D was dissolved in methanol (15 mL) and 1 Nhydrochloric acid (100 mL) and then heated at reflux for 2 hours. Thereaction mixture was concentrated under vacuum to a volume of about 50mL. Addition of concentrated ammonium hydroxide to pH 12 did not producea precipitate. The pH was adjusted to 7 with 1 N hydrochloric acid. Themixture was extracted with dichloromethane and then with ethyl acetate.The aqueous layer was concentrated to dryness. The residue was dissolvedin water (50 mL) and then extracted continuously with refluxingchloroform for 36 hours. The chloroform extract was concentrated undervacuum to provide a light tan solid. This material was recrystallizedfrom acetonitrile to provide 2.5 g of1-(4-aminobutyl)-2-phenyl-1H-imidazo[4,5-c]quinolin-4-amine as an offwhite solid, m.p. 175-177° C. Analysis: Calculated for C₂₀H₂₁N₅: %C,72.48; %H, 6.39; %N, 21.13; Found: %C, 72.72; %H, 6.32; %N, 20.71.

Part F

According to the general method of Example 61,1-(4-aminobutyl)-2-phenyl-1H-imidazo[4,5-c]quinolin-4-amine andnicotinoyl chloride hydrochloride were combined to provideN³-[4-(4-amino-2-phenyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]nicotinamideas a white crystalline solid, m.p. 84.5-86.1° C. ¹H NMR (300 MHz,DMSO-d₆) δ8.91 (s, 1H), 8.69 (m, 1H), 8.56 (m, 1H), 8.07 (m, 2H),7.75-7.41 (m, 8H), 7.21 (m, 1H), 6.72 (broad s, 2H), 4.60 (m, 2H), 3.15(t, J=6.0 Hz, 2H), 1.86 (m, 2H), 1.40 (m, 2H); MS (CI) m/e 437 (M+H).

EXAMPLE 67

N-[4-(4-Amino-2-phenyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-quinolinecarboxamide

According to the general method of Example 61,1-(4-aminobutyl)-2-phenyl-1H-imidazo[4,5-c]quinolin-4-amine andquinoline-2-carbonyl chloride were combined to provideN-[4-(4-amino-2-phenyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-quinolinecarboxamideas an off white crystalline solid, m.p. 81.1-83.9° C. ¹H NMR (300 MHz,DMSO-d₆) δ8.90 (t, J=6.0 Hz, 1H), 8.55 (d, J=8.5 Hz, 1H), 8.12-8.07 (m,4H), 7.90-7.84 (m, 1H), 7.75-7.54 (m, 7H), 7.36 (t, J=7.5 Hz, 1H), 7.18(t, J=7.5 Hz, 1H), 6.70 (broad s, 2H), 4.61 (m, 2H), 3.23 (m, 2H), 1.88(m, 2H), 1.49 (m, 2H); MS (CI) m/e 487 (M+H).

EXAMPLES 68-102

The compounds shown in the table below were prepared using the syntheticmethod described in Reaction Scheme II above.

A solution of 1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (36μmol) in 10 mL of dichloromethane in a screw-capped test tube was cooleddown to −5° C. The acid chloride (45 μmol) was added as a 0.3 M solutionin dichloromethane. Argon was bubbled through the mixture duringaddition and for an additional 15 seconds, and the mixture was allowedto stand at −5° C. overnight. To this mixture was added approximately 90mg of an aminomethyl polystyrene resin (0.62 meq/g, 100-200 mesh), andthe mixture was warmed to reflux and shaken at 600 rpm for 3 hours. Thecompounds were purified by eluting through a short plug of silica gelwith 10:1 dichloromethane-methanol, collecting ca. 1 mL fractions andpooling the product fractions (fractions analyzed by tic in 9:1dichloromethane-methanol to identify product). Compounds were analyzedby 500 MHz ¹H nmr and APCI-MS (plug injection or an LC/MS protocol).

Ex- am- APCI- ple MS No. Structure m/e 500 MHz ¹H NMR 68

450.10 (DMSO-d₆)δ8.93(t, J=5.2Hz, 1H), 8.23(s, 1H), 8.06 (d, J=8.2Hz,1H), 7.63(d, J=8.5Hz, 1H), 7.46(t, J=7.8Hz, 1H), 7.27(t, J=7.6Hz, 1H),6.75(bs, 2H), 4.65(t, J=7Hz, 2H), 3.31(q, J=6Hz, 2H), 1.92(quintet,J=8Hz, 2H), 1.56 (quintet, J=7Hz, 2H) 69

394.12 (DMSO-d₆)δ8.40(t, J=5.8Hz, 1H), 8.23(s, 1H), 8.08 (d, J=8.2Hz,1H), 7.64(d, J=8.5Hz, 1H), 7.47(t, J=8.2Hz, 1H), 7.43(d, J=7.9Hz, 1H),7.39(dt, J=1.5Hz, J=7Hz, 1H), 7.30(t, J=6.4Hz, 1H), 7.28(t, J=10.4Hz,1H), 7.23(dd, J= 1.5Hz, J=7.3Hz, 1H), 6.75(bs, 2H), 4.65(t, J=7Hz, 2H),3.26(q, J=6Hz, 2H), 1.95(quintet, J=8Hz, #2H), 1.56 (quintet, J=7.5Hz,2H) 70

428.07 (DMSO-d₆)δ8.47(t, J=5.8Hz, 1H), 8.22(s, 1H), 8.07 (d, J=8.2Hz,1H), 7.64(d, J=8.8Hz, 1H), 7.63 (d, J=2.1Hz, 1H), 7.47(t, J=8.2Hz, 1H),7.40(dd, J=2.1Hz, J=10.4Hz, 1H), 7.29(t, J=7.0Hz, 1H), 7.26(d, J=8.2Hz,1H), 6.75(bs, 2H), 4.65(t, J=5.5Hz, 2H), 3.25(q, J=6.5Hz, 2H),1.94(quintet, J=8Hz, 2H), 1.54(quintet, J=7Hz, 2H), 71

428.06 (DMSO-d₆)δ8.65(t, J=6.1Hz, 1H), 8.23(s, 1H), 8.08 (d, J=7.9Hz,1H), 7.64(d, J=8.2Hz, 1H), 7.47(t, J=7.9Hz, 1H), 7.43(d, J=9Hz, 1H),7.44(d, J=7Hz, 1H), 7.38 (dd, J=9.2Hz, J=7Hz, 1H), 7.28(t, J=7.9Hz, 1H),6.8(bs, 2H), 4.65(t, J=6.5Hz, 2H), 3.28(m, 2H), 1.96 (quintet, J=7.5Hz,2H), 1.57(quintet, J=8Hz, 2H) 72

378.11 (DMSO-d₆)δ8.50(t, J=5.8Hz, 1H), 8.23(s, 1H), 8.04 (d, J=8.2Hz,1H), 7.84(dd, J=2.1Hz, J=5.8Hz, 2H), 7.62 (d, J=7.3Hz, 1H), 7.44(t,J=7Hz, 1H), 7.26(t, J=6.7Hz, 2H), 7.22(t, J=8.2Hz, 1H), 6.74(bs, 2H),4.63(t, J=7Hz, 2H), 3.28(m, 2H), 1.91(quintet, J=7.5Hz, 2H), 1.57(quintet, J=8Hz, 2H) 73

394.07 (DMSO-d₆)δ8.56(t, J=5.6Hz, 1H), 8.24(s, 1H), 8.05 (d, J=7.9Hz,1H), 7.79(d, J=8.5Hz, 2H), 7.63 (d, J=8.2Hz, 1H), 7.50(d, J=8.9Hz, 2H),7.46(t, J=7.6Hz, 1H), 7.23(t, J=7.6Hz, 1H), 6.8(bs, 2H), 4.64(t, J=7Hz,2H), 3.29(q, J=6.5Hz, 2H), 1.91(quintet, J=7.5Hz, 2H), 1.57 (quintet,J=7.5Hz, 2H) 74

390.13 (DMSO-d₆)δ8.33(t, J=5.6Hz, 1H), 8.24(s, 1H), 8.05 (d, J=8.2Hz,1H), 7.76(d, J=8.8Hz, 2H), 7.63 (d, J=8.2Hz, 1H), 7.45(t, J=8.2Hz, 1H),7.24(t, J=7.9Hz, 1H), 6.95(d, J=8.8Hz, 2H), 6.81(bs, 2H), 4.64(t, J=7Hz,2H), 3.80(s, 3H), 3.28(quintet, J=5.5Hz, 2H), 1.90 (quintet, J=8Hz, 2H),1.57(quintet, J=8.5Hz, 2H) 75

428.10 (DMSO-d₆)δ8.71(t, J=5.6Hz, 1H), 8.27(s, 1H), 8.06 (d, J=7.9Hz,1H), 7.96(d, J=8.2Hz, 2H), 7.64 (d, J=7.9Hz, 2H), 7.64(d, J=7.9Hz, 1H),7.46(t, J=7.3Hz, 1H), 7.25(t, J=7Hz, 1H), 6.9(bs, 2H), 4.65(t, J=7Hz,2H), 3.31(m, 2H), 1.92(quintet, J=8Hz, 2H), 1.59 (quintet, J=7.5Hz, 2H)76

416.22 (DMSO-d₆)δ8.54(s, 1H), 8.39(t, J=5.5Hz, 1H), 8.22 (d, J=8.2Hz,1H), 7.82(d, J=8.2Hz, 1H), 7.70(t, J=4Hz, 1H), 7.68(d, J=4.3Hz, 2H),7.52(t, J=8Hz, 1H), 7.43 (d, J=7.8Hz, 2H), 4.72(t, J=7Hz, 2H), 3.30(q,J=6.5Hz, 2H), 1.91(quintet, J=7.5Hz, 2H), 1.59(quintet, J=7.5Hz, 2H),1.29(s, 9H) 77

374.18 (DMSO-d₆)δ8.54(s, 1H), 8.38(t, J=5.8Hz, 1H), 8.23 (d, J=8.2Hz,1H), 7.82(d, J=8.6Hz, 1H), 7.71(t, J=8.2Hz, 1H), 7.659(d, J=8.2Hz, 2H),7.54(t, J=8.2Hz, 1H), 7.22 (d, J=7.9Hz, 2H), 4.71(t, J=6.5Hz, 2H),3.28(q, J=6Hz, 2H), 2.34(s, 3H), 1.92(quintet, J=8Hz, 2H), 1.60(quintet, J=7.5Hz, 2H) 78

374.18 (DMSO-d₆)δ8.50(s, 1H), 8.22(d, J=8.2Hz, 1H), 8.06 (t, J=5.8Hz,1H), 7.84(d, J=8.5Hz, 1H), 7.74(t, J=7Hz, 1H), 7.58, (t, J=7.6Hz, 1H),7.21(m, 2H), 7.18(m, 3H), 4.67 (t, J=7Hz, 2H), 3.33(s, 2H), 3.09(q,J=6Hz, 2H), 1.84 (quintet, J=8Hz, 2H), 1.48(quintet, J=7.5Hz, 2H) 79

386.15 (DMSO-d₆)δ8.55(s, 1H), 8.24(d, J=8.2Hz, 1H), 8.16 (t, J=5.8Hz,1H), 7.82(d, J=8.6Hz, 1H), 7.72(t, J=7.3Hz, 1H), 7.58(t, J=7.3Hz, 1H),7.53(d, J=6.7Hz, 2H), 7.40(m, 4H), 6.57(d, J=15.9Hz, 1H), 4.72(t, J=7Hz,2H), 3.23 (q, J=6Hz, 2H), 1.91(quintet, J=7.5Hz, 2H), 1.55 (quintet,J=7.5Hz, 2H) 80

354.19 (DMSO-d₆)δ8.53(s, 1H), 8.24(d, J=8.2Hz, 1H), 7.83 (d, J=8.2Hz,1H), 7.74(m, 2H), 7.58(t, J=7.8, 1H), 4.70 (t, J=7Hz, 2H), 3.06(q,J=6Hz, 2H), 1.86(s, 2H), 1.86 (quintet, J=8.5Hz, 2H), 1.44(quintet,J=7.5Hz, 2H), 0.84 (s, 9H) 81

324.15 (DMSO-d₆)δ8.53(s, 1H), 8.23(d, J=8.5Hz, 1H), 8.06 (t, J=5.5Hz,1H), 7.84(d, J=8.2Hz, 1H), 7.74(t, J=8.2Hz, 1H), 7.59(t, J=8.2Hz, 1H),4.69(t, J=7Hz, 2H), 3.09 (q, J=6Hz, 2H), 1.86(quintet, J=7Hz, 2H),1.47(m, 3H), 0.59(m, 4H) 82

352.16 (DMSO-d₆)δ8.52(s, 1H), 8.23(d, J=7.9Hz, 1H), 7.83 (d, J=8.2Hz,1H), 7.74(m, 2H), 7.60(t, J=7.6Hz, 1H), 4.69 (t, J=7.5Hz, 2H), 3.06(q,J=6Hz, 2H), 2.42 (quintet, J=8Hz, 1H), 1.84(quintet, J=7.5Hz, 2H), 1.59(m, 2H), 1.55(m, 2H), 1.48(m, 6H) 83

380.16 (DMSO-d₆)δ8.52(s, 1H), 8.22(d, J=8.2Hz, 1H), 7.83 (d, J=8.2Hz,1H), 7.77(t, J=5.8Hz, 1H), 7.73(t, J=8.2Hz, 1H), 7.58(t, J=8.2Hz, 1H),4.68(t, J=7Hz, 2H), 3.06 (q, J=6Hz, 2H), 1.98(t, J=8Hz, 2H), 1.84(quintet, J=7.5Hz, 2H), 1.62(m, 3H), 1.48(m, 8H), 0.97 (m, 2H) 84

366.15 (DMSO-d₆)δ9.2(b, 2H), 8.52(s, 1H), 8.22(d, J=8.2Hz, 1H), 7.83(d,J=8.5Hz, 1H), 7.74(t, J=8.2Hz, 1H), 7.65 (t, J=5.8Hz, 1H), 7.58(t,J=7.9Hz, 1H), 4.68(t, J=7Hz, 2H), 3.04(q, J=6.5Hz, 2H), 1.95(m, 1H),1.83 (quintet, J=8Hz, 2H), 1.60(m, 3H), 1.50(m, 2H), 1.43 (quintet,J=7.5Hz, 2H), 1.14(m, 5H) 85

350.18 (DMSO-d₆)δ9.0(bs, 2H), 8.54(s, 1H), 8.39(t, J=5Hz, 1H), 8.22(d,J=5Hz, 1H), 7.82(d, J=10Hz, 1H), 7.80(s, 1H, 7.72 (t, J=10Hz, 1H),7.54(t, J=10Hz, 1H), 7.02(dd, J=1Hz, J=3Hz, 1H), 6.60(dd, J=1.7Hz,J=3.5Hz, 1H), 4.70 (t, J=7.5Hz, 2H), 3.25(q, J=6Hz, 2H), 1.90 (quintet,J=7.5Hz, 2H), 1.58(quintet, J=7Hz, 2H) 86

366.25 (DMSO-d₆)δ8.51(t, J=5.5Hz, 1H), 8.32(s, 1H), 8.10 (d, J=8.6Hz,1H), 7.72(dd, J=0.9Hz, J=4.9Hz, 1H), 7.68 (m, 2H), 7.52(t, J=7.9Hz, 1H),7.34(bs, 2H), 7.31 (t, J=7.9Hz, 1H), 7.11(dd, J=4Hz, J=4.9Hz, 1H), 4.66(t, J=7.5Hz, 2H), 3.27(q, J=6Hz, 2H), 1.91 (quintet, J=7.5Hz, 2H),1.58(quintet, J=8Hz, 2H) 87

405.21 (DMSO-d₆)δ8.80(t, J=5.8Hz, 1H), 8.28(s, 1H), 8.27 (d, J=8.6Hz,2H), 8.07(d, J=8Hz, 1H), 7.98(d, J=8.9Hz, 2H), 7.65(d, J=8.6Hz, 1H),7.47(t, J=7.9Hz, 1H), 7.27 (t, J=7.9Hz, 1H), 7.07(bs, 2H), 4.66(t,J=7Hz, 2H), 1.93 (quintet, J=8Hz, 2H), 1.60(quintet, J=7.5Hz, 2H) 88

298.16 (DMSO-d₆)δ8.33(s, 1H), 8.11(d, J=8.1Hz, 1H), 7.83 (t, J=6Hz, 1H),7.71(d, J=8.1Hz, 1H), 7.56(t, J=8.1Hz, 1H), 7.39(t, J=7.8Hz, 1H),4.63(t, J=7Hz, 2H), 3.05 (q, J=6.5Hz, 2H), 1.85(quintet, J=7.5Hz, 2H),1.74(s, 3H), 1.44(quintet, J=7.5Hz, 2H) 89

439.30 (DMSO-d₆)δ8.59(t, 1H), 8.43(s, 1H), 8.16 (d, J=7.6Hz, 1H),7.94(d, J=1.7Hz, 1H), 7.75(t, J=6.8Hz, 2H), 7.71(d, J=8.1Hz, 1H),7.60(m, 1H), 7.40(t, J=7.8Hz, 2H), 4.68(t, J=6.5Hz, 2H), 3.30(q, J=6Hz,2H), 1.91 (quintet, J=6Hz, 2H), 1.59(quintet, J=6Hz, 2H) 90

418.28 (DMSO-d₆)δ8.29(s, 1H), 8.08(d, J=8.5Hz, 1H), 7.68 (d, J=7.8Hz,1H), 7.53(t, J=7.6Hz, 1H), 7.36(t, J=7.3Hz, 1H), 7.30(t, J=5.9Hz, 1H),4.62(t, J=6.5Hz, 2H), 3.05 (q, J=6.5Hz, 2H), 1.86(m, 5H), 1.60(m, 12H),1.41 (quintet, J=7Hz, 2H) 91

462.21 (DMSO-d₆)δ8.25(s, 1H), 8.06(d, J=8.3Hz, 1H), 7.70 (d, J=8.1Hz,1H), 7.55(t, J=7.8Hz, 1H), 7.49(t, J=5.6Hz, 1H), 7.37(t, J=7.3Hz, 1H),7.24(s, 4H), 4.57(t, J=7Hz, 2H), 3.01(q, J=6Hz, 2H), 2.38(m, 2H),1.68(m, 4H), 1.49(m, 2H), 1.40(m, 4H) 92

422.28 (DMSO-d₆)δ8.36(s, 1H), 8.13(d, J=8.8Hz, 1H), 7.86 (b, 2H),7.76(t, J=6Hz, 1H), 7.74(d, J=8.5Hz, 1H), 7.59 (t, J=8.1Hz, 1H), 7.43(t,J=7.5Hz, 1H), 5.77(m, 1H), 4.98 (dd, J=2Hz, J=17Hz, 1H), 4.92(dd ,J=1.5Hz, J=10Hz, 1H), 4.64(t, J=7Hz, 2H), 3.07(q, J=5.5Hz, 2H), #1.97(m, J=7.5Hz, 4H), 1.84(quintet, J=7Hz, 2H), 1.45 (quintet, J=8Hz, 2H),1.40(quintet, J=6.5Hz, 2H), 1.30 (quintet, J=7Hz, 2H), 1.18(m, 8H) 93

450.19 (DMSO-d₆)δ8.43(t, J=5.6Hz, 1H), 8.31(s, 1H), 8.08 (d, J=7.8Hz,1H), 7.67(d, J=8.1Hz, 1H), 7.50(t, J=7.3Hz, 1H), 7.29(t, J=7.8Hz, 1H),7.11(s, 2H), 4.67(t, J=7Hz,2H), 3.78(s, 6H), 3.69(s, 3H), 3.29(q, J=6Hz,2H), 1.91 (quintet, J=7.5Hz, 2H), 1.58(quintet, J=7.5Hz, 2H) 94

402.25 (DMSO-d₆)δ8.24(s, 1H), 8.19(t, J=5.9Hz, 1H), 8.08 (d, J=8Hz, 1H),7.65(d, J=8.3Hz, 1H), 7.48(t, J=8.3Hz, 1H), 7.29(t, J=7.8Hz, 1H),6.87(bs, 2H), 6.77(s, 2H), 4.65 (t, J=6.5Hz, 2H), 3.26(q, J=6.5Hz, 2H),2.19(s, 3H), 2.02 (s, 6H), 1.92(quintet, J=8Hz, 2H), 1.54(quintet,J=8.5Hz, 2H) 95

398.21 (DMSO-d₆)δ8.28(s, 1H), 8.08(d, J=7.6Hz, 1H), 7.79 (t, J=5.9Hz,1H), 7.68(d, J=7.8Hz, 1H), 7.52(t, J=7.6Hz, 1H), 7.35(t, J=7.1Hz, 1H),7.2(bs, 2H), 4.62(t, J=7Hz, 2H), 3.56(s, 3H), 3.06(q, J=5.5Hz, 2H),2.24(m, 2H), 1.99 (quintet, J=6.5Hz, 2H), 1.84(quintet, J=8Hz, 2H), 1.43(m, 6H) 96

395.12 (DMSO-d₆)δ8.88(t, J=5.6Hz, 1H), 8.25(s, 1H), 8.05 (d, J=8.3Hz,1H), 7.72(d, J=3.9Hz, 1H), 7.63 (d, J=8.3Hz, 1H), 7.45(t, J=7.3Hz, 1H),7.32(d, J=3.9Hz, 1H), 7.26(t, J=7.1Hz, 1H), 6.93(bs, 2H), 4.64(t, J=7Hz,2H), 3.28(q, J=6Hz, 2H), 1.90(quintet, J=7Hz, 2H), 1.56 (quintet, J=8Hz,2H) 97

395.20 (DMSO-d₆)δ8.57(t, J=5.6Hz, 1H), 8.42(dd, J=1.9Hz, J=4.6Hz, 1H),8.25(s, 1H), 8.12(d, J=8.0Hz, 1H), 7.70 (dd, J=2Hz, J=7.6Hz, 1H),7.65(d, J=8.5Hz, 1H), 7.49 (t, J=7.6Hz, 1H), 7.41(dd, J=4.9Hz, J=7.6Hz,1H), 7.30 (t, J=7.6Hz, 1H), 6.90(bs, 2H), 4.66(t, J=7Hz, 2H), 3.27 (q,J=6.5Hz, 2H), 1.96(quintet, J=8.5Hz, 2H), 1.56 (quintet, J=7.5Hz, 2H) 98

404.18 (DMSO-d₆)δ8.36(s, 1H), 8.14(d, J=8.3Hz, 1H), 7.97 (t, J=5.6Hz,1H), 7.76(d, J=8.3Hz, 1H), 7.62(t, J=7.8Hz, 1H), 7.45(t, J=7.5Hz, 1H),7.08(d, J=8.5Hz, 2H), 6.76 (d, J=8.8Hz, 2H), 4.63(t, J=7Hz, 2H), 3.70(s,3H), 3.25 (s, 2H), 3.08(q, J=6Hz, 2H), 1.83(quintet, J=7.5Hz, 2H),1.46(quintet, J=7Hz, 2H) 99

366.22 (DMSO-d₆)δ8.35(s, 1H), 8.2(bs, 1H), 8.13 (d, J=7.8Hz, 1H),7.75(t, J=5.6Hz, 1H), 7.73(d, J=8.8Hz, 1H), 7.59(t, J=7.6Hz, 1H),7.42(t, J=7.6Hz, 1H), 4.65 (t, J=7Hz, 2H), 3.06(q, J=6Hz, 2H), 2.02(m,J=7.5Hz, 1H), 1.96(d, J=7.5Hz, 2H), 1.84(quintet, J=8Hz, 2H), 1.55(quintet, J=5Hz, 2H), 1.46(m, J=7.5Hz, 6H), 1.00 (m, J=12Hz, 2H) 100 

418.11 (DMSO-d₆)δ9.6-8.5(b, 2H), 8.66(t, J=5.5Hz, 1H), 8.54 (s, 1H),8.23(d, J=8.0Hz, 1H), 8.00(d, J=8.0Hz, 2H), 7.87 (d, J=8.0Hz, 2H),7.81(d, J=8Hz, 1H), 7.70(t, J=8.0 Hz, 1H), 7.53(t, J=8.0Hz, 1H), 4.72(t,J=7.0Hz, 2H), 3.88(s, 3H), 3.31(q, J=5.5Hz, 2H), 1.93(quintet, J=7.0,2H), 1.61 (quintet, J=7.0Hz, 2H) 101 

454.19 (DMSO-d₆)δ9.6-8.6(b, 2H), 8.51(s, 1H), 8.22 (d, J=8.5Hz, 1H),7.84(d, J=8.5Hz, 1H), 7.78(t, J=5.5 Hz, 1H), 7.73(t, J=8.5Hz, 1H),7.58(t, J=8.5Hz, 1H), 4.68 (t, J=7.0Hz, 2H), 3.57(s, 3H), 3.07(q,J=5.5Hz, 2H), 2.26 (t, J=7.0Hz, 2H), 1.84(quintet, J=7.0Hz, 2H), #1.48(sextet, J=7.0Hz, 4H), 1.38(quintet, J=7.0Hz, 2H), 1.71 (m, 8H) 102

444.11 Compound is trifluoroacetate salt

EXAMPLES 103-107

The compounds shown in the Table below were prepared according to thesynthetic method described below.

A 10 mg (25 μmol) portion ofN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-(chloromethyl)benzamide(example 7) was dissolved in 1 mL of N,N-dimethylformamide in ascrew-cap tube, and the appropriate amine (2 eq) was added, along withca. 70 mg (270 μmol) of N,N-(diisopropyl)aminomethylpolystyrene beads(PS-DIEA, 3.86 meq/g, Argonaut). The mixture was heated to 50° C. andwas vortexed overnight at 500 rpm. Another 1-2 eq of amine was added andthen heating and vortexing was continued for a second night. The productwas isolated by injection of the filtered reaction mixture onto asemi-prep HPLC system (Shimadzu LC-6A pumps, Rainin Microsorb C18column, 21.4×250 mm, 8 micron particle size, 60A pore, 9.9 mL/min.,gradient elution from 2-95% B in 25 min., hold at 95% B for 5 min.,where A=0. 1% trifluoroacetic acid/water and B=0.1% trifluoroaceticacid/acetonitrile, peak detection at 254 nm, collected 5 mL fractions).The semi-prep hplc fractions were analyzed by reversed-phase hplc andthe appropriate fractions were dried in vacuo to provide the compound asa trifluoroacetate salt. The compound was dissolved in ca. 3-5 mL of 2:1dichloromethane-methanol and shaken with ca. 80 mg (300 μmol) ofdiisopropylaminomethyl-polystyrene resin (Argonaut PS-DIEA, 3.86 mmol/g)for 1-2 h to liberate the free amine, and then filtered and dried invacuo to give the compound as an amorphous solid. Each amine product wasanalyzed by LC/APCI-MS.

Example APCI-MS No. Structure of the Free Base m/e 103

459.26 104

624.51 105

480.34 106

523.31 107

508.32

EXAMPLE 108

N¹-(4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl)-2-(2-thienyl)acetamide

This compound was prepared according to the method of Examples 68-102.(DMSO-d₆) δ8.28 (s, 1H), 8.09 (m,2H), 7.70 (d,J=7.9 Hz,1H), 7.54(t,J=7.9 Hz,1H), 7.36 (t,J=7.3Hz, 1H), 7.28 (dd,J=0.9 Hz, J=5.2 Hz,1H),6.88 (dd,J=3.4 Hz, J=5.2 Hz,1H), 6.82 (d,J=3.1 Hz, 1H), 4.63 (t,J=7 Hz,2H), 3.56 (s,2H), 3.10 (q,J=6.5 Hz,2H), 1.85 (quintet,J=7.5 Hz,2H), 1.46(quintet,J=7.5 Hz,2H) MS (APCI) m/e 380.22 (M+H).

Examples 109-119

The examples in the table below were prepared using the synthetic methoddescribed in Reaction Scheme III.

1-(4-Aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (10 mg, 0.04 mmol)was suspended in 10 mL of dichloromethane in a threaded test tube. Theacid (0.05 mmol) was added and the mixture was briefly vortexed. To themixture was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimidehydrochloride (EDC, 10 mg, 0.05 mmol) and the mixture was shakenovernight at ambient temperature. To the tube was added about 90 mg ofaminomethylpolystrene resin (Bachem, ˜1 meq/g, 100-200 mesh) and themixtures were heated to reflux and shaken overnight. The mixture wasthen filtered to remove the resin, and was purified by semi-preparativereversed-phase HPLC (Rainin Microsorb C18 column, 21.4×250 mm, 8 micronparticle size, 60A pore, 10 mL/min., gradient elution from 2-95% B in 25min., hold at 95% B for 5 min., where A=0.1% trifluoroacetic acid/waterand B=0.1% trifluoroacetic acid/acetonitrile, peak detection at 254 nmfor triggering fraction collection). The semi-prep HPLC fractions wereanalyzed by LC-APCI/MS and the appropriate fractions were combined andlyophilized to provide the trifluoroacetate salt of the desired amide.The compounds were analyzed by LC-MS (APCI).

Example Number Structure of Free Base Observed Mass 109

464.18 110

364.15 111

427.98, 429.97 112

323.19 113

370.18 114

452.10 115

336.16 116

338.20 117

384.20 118

368.28 119

420.30

EXAMPLES 120-146

The examples in the table below were prepared using the synthetic methoddescribed in Reaction Scheme V above.

Part A

1-(4-Aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (25 mg, 0.1 mmol) wassuspended in 5 mL of dichloromethane in a threaded test tube and thealdehyde (about 0.1 mmol) was added. The mixture was heated to refluxand was vortexed at 500 rpm for half an hour. The mixture was allowed tocool for a few minutes and then sodium triacetoxyborohydride (38 mg,0.18 mmol) was added. The mixture was shaken at ambient temperature for3 days, then was quenched with 0.5 mL of methanol and evaporated todryness. The mixture was purified by semi-preparative reversed-phaseHPLC (Rainin Microsorb C1 8 column, 21.4×250 mm, 8 micron particle size,60A pore, 10 mL/min., gradient elution from 2-95% B in 25 min., hold at95% B for 5 min., where A=0. 1% trifluoroacetic acid/water and B=0.1%trifluoroacetic acid/acetonitrile, peak detection at 254 nm fortriggering fraction collection). The semi-prep HPLC fractions wereanalyzed by LC-APCI/MS and the appropriate fractions were combined andlyophilized to provide the trifluoroacetate salt of the desiredsecondary amine. The compounds were analyzed by LC-MS (APCI).

Part B

The secondary amines from Part A (about 3-30 μmol as thedi-trifluoroacetate salt) were each dissolved in 1 mL of pyridine, andabout 10 equivalents of a 0.1 M solution of acetic anhydride indichloromethane was added. The mixtures were allowed to stand for 1 hourand then 200 μL of methanol was added. The mixtures were evaporated todryness in a vacuum centrifuge. The mixtures were purified bysemi-preparative reversed-phase HPLC as in Part A. The compounds wereanalyzed by LC-MS (APCI).

Example Number Structure of Free Base Observed Mass 120

418.1 121

466.0, 468.0 122

482.0, 484   123

460.1 124

422.0 125

467.0, 469.0 126

467.0, 469.0 127

530.0 128

456.0, 458.0 129

424.0 130

448.1 131

448.1 132

416.1 133

406.1 134

378.0 135

378.0 136

416.1 137

410.0 138

438.0 139

468.1 140

433.0 141

433.0 142

512.0 143

389.0 144

402.1 145

478.1 146

478.1

EXAMPLES 147-159

The compounds in the table below were prepared using the syntheticmethod of Reaction Scheme II above.

1-(4-Aminobutyl)-2-methoxyethyl-1H-imidazo[4,5-c]quinolin-4-amine (50mg) was placed in a 2 dram (7.4 mL) vial. Diisopropylethylamine (1.2eq)and dichloromethane (1 mL) were added. A solution containing thecarboxylic acid chloride (1.1 eq) in dichloromethane (1 mL) was added.The vial was placed on a shaker for about 2 hours at ambienttemperature. The reaction mixture was analyzed by LC/MS to confirm theformation of the desired product. The solvent was removed and theresidue was purified by semi-preparative HPLC (Capcell PakC 18 column,35×20 mm, 5 micron particle size, 20 mL/min., gradient elution from5-95% B in 10 min., hold at 95% B for 2 min., where A=0.1%trifluoroacetic acid/water and B=0.1% trifluoroacetic acid/acetonitrile,peak detection at 254 nm for triggering fraction collection). Thesemi-prep HPLC fractions were analyzed by LC-APCI/MS and the appropriatefractions were combined and lyophilized to provide the trifluoroacetatesalt of the desired amide.

Example # Structure of the Free Base APCI-MS m/e 147

384.2 148

396.2 149

410.2 150

424.2 151

432.2 152

432.3 153

458.2 154

468.2 155

468.2 156

474.2 157

476.3 158

478.3 159

484.30

EXAMPLES 160-168

The compounds in the table below were prepared using the syntheticmethod of Reaction Scheme III above.

1-(4-Aminobutyl)-2-methoxyethyl-1H-imidazo[4,5-c]quinolin-4-amine (50mg), the carboxylic acid (1.0 eq.) and dichloromethane (3 mL) wereplaced in a 2 dram (7.4 mL) vial. A solution containing1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (1.1 eq)in dichloromethane (1 mL) was added. The vial was placed on a shaker forabout 2 hours at ambient temperature. The reaction mixture was analyzedby LC/MS to confirm the formation of the desired product. The solventwas removed and the residue was purified by semi-preparative HPLC(Capcell Pak C18 column, 35×20 mm, 5 micron particle size, 20 mL/min.,gradient elution from 5-95% B in 10 min., hold at 95% B for 2 min.,where A=0.1% trifluoroacetic acid/water and B=0.1% trifluoroaceticacid/acetonitrile, peak detection at 254 nm for triggering fractioncollection). The semi-prep HPLC fractions were analyzed by LC-APCI/MSand the appropriate fractions were combined and lyophilized to providethe trifluoroacetate salt of the desired amide.

Example # Structure of Free Base APCI-MS m/e 160

381.2 161

382.2 162

408.3 163

426.2 164

434.2 165

440.2 166

478.2 167

492.3 168

500.2, 502.2

EXAMPLE 169N¹-[4-(4-Amino-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-1yl)butyl]acetamideTrifluoroacetate

Using the method of Examples 147-159 above,1-(4-aminobutyl)-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-4-aminewas reacted with acetyl chloride to provideN¹-[4-(4-amino-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-1-yl)butyl]acetamideTrifluoroacetate. APCI-MS m/e 418.2.

EXAMPLES 170 & 171

The examples in the table below were prepared by reacting1-(4-aminobutyl)-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-4-aminewith the appropriate carboxylic acid using the method of Example160-168.

Ex- am- ple APCI- # Structure of the Free Base MS m/e 170

481.2 171

481.2

EXAMPLES 172-174

The examples in the table below were prepared according to the syntheticmethod described in Reaction Scheme VI above.

Part A

A catalytic amount of platinum (IV) oxide was added to a solution of1-(4-aminobutyl)-2-methoxyethyl-1H-imidazo[4,5-c]quinolin-4-amine (7.7g, 24.5 mmol) in trifluoroacetic acid (250 mL). The reaction mixture washydrogenated at 50 psi (3.44×10⁵ Pa) on a Parr apparatus. The progressof the reaction was monitored by LC/MS. Additional catalyst was added 7,11, and 17 days after the start of the reaction. After 25 days thereaction was complete. The reaction mixture was filtered through a layerof Celite® filter aid to remove the catalyst and the filtrate wasconcentrated under vacuum. The residue was combined with 1 Nhydrochloric acid (100 mL) and stirred overnight. The mixture was madebasic (pH=11) with ammonium hydroxide and then extracted withdichloromethane (3×300 mL). The extracts were combined and concentratedunder vacuum to provide 3.5 g of1-(4-aminobutyl)-6,7,8,9-tetrahydro-2-methoxyethyl-1H-imidazo[4,5-c]quinolin-4-amineas a solid.

Part B

Using the method of Examples DC 147-159 above. The material from Part Awas reacted with the appropriate acid chloride to give the desiredamide.

Example # Structure of the Free Base APCI-MS m/e 172

422.2 173

423.1 174

436.2

EXAMPLES 175-180

The examples in the table below were prepared according to the syntheticmethod of Reaction Scheme III above using the general method of Examples160-168.

Example # Structure of the Free Base mass 175

408.2 176

419.1 177

438.2 178

446.2 179

453.2 180

480.2

CYTOKINE INDUCTION IN HUMAN CELLS

An in vitro human blood cell system was used to assess cytokineinduction by compounds of the invention. Activity is based on themeasurement of interferon and tumor necrosis factor (α) (IFN and TNF,respectively) secreted into culture media as described by Testerman et.al. In “Cytokine Induction by the Immunomodulators Imiquimod andS-27609”, Journal of Leukocyte Biology, 58, 365-372 (September, 1995).

Blood Cell Preparation for Culture

Whole blood is collected by venipuncture into EDTA vacutainer tubes fromhealthy human donors. Peripheral blood mononuclear cells (PBMCs) areseparated from whole blood by density gradient centrifugation usingHistopaque®-1077 (Sigma Chemicals, St. Louis, Mo.). The PBMCs aresuspended at 3-4×10⁶ cells/mL in RPMI 1640 medium containing 10% fetalbovine serum, 2 mM L-glutamine and 1% penicillin/streptomycin solution(RPMI complete). The PBMC suspension is added to 48 well flat bottomsterile tissue culture plates (Costar, Cambridge, Mass. or BectonDickinson Labware, Lincoln Park, N.J.) containing an equal volume ofRPMI complete media containing test compound.

Compound Preparation

The compounds are solubilized in dimethyl sulfoxide (DMSO). The DMSOconcentration should not exceed a final concentration of 1% for additionto the culture wells.

Incubation

The solution of test compound is added at 60 μM to the first wellcontaining RPMI complete and serial (three fold or ten fold) dilutionsare made. The PBMC suspension is then added to the wells in an equalvolume, bringing the test compound concentrations to the desired range.The final concentration of PBMC suspension is 1.5-2×10⁶ cells/mL. Theplates are covered with sterile plastic lids, mixed gently and thenincubated for 18 to 24 hours at 37° C. in a 5% carbon dioxideatmosphere.

Separation

Following incubation the plates are centrifuged for 5-10 minutes at 1000rpm (˜200×g) at 4° C. The cell culture supernatant is removed with asterile polypropylene pipet and transferred to sterile polypropylenetubes. Samples are maintained at −30 to −70° C. until analysis. Thesamples are analyzed for interferon (α) by either ELISA or bioassay andfor tumor necrosis factor (α) by ELISA.

Interferon Bioassay Analysis

Interferon is determined by bioassay using A549 human lung carcinomacells challenged with encephalomyocarditis. The details of the bioassaymethod have been described by G. L. Brennan and L. H. Kronenberg in“Automated Bioassay of Interferons in Micro-test Plates”, Biotechniques,June/July, 78, 1983, incorporated herein by reference. Briefly statedthe method is as follows: A549 cells are incubated with dilutions ofsamples or a standard interferon at 37° C. for 24 hours. The incubatedcells are then infected with an inoculum of encephalomyocarditis virus.The infected cells are incubated for an additional 24 hours at 37° C.before evaluating for viral cytopathic effect. The viral cytopathiceffect is quantified by staining with crystal violet followed by visualscoring of the plates. Results are expressed as alpha reference units/mLbased on the value obtained for NIH Human Leukocyte IFN standard.

Interferon (α) and Tumor Necrosis Factor (α) Analysis by ELISA

Interferon (α) concentration is determined by ELISA using a HumanMulti-Species kit from PBL Biomedical Laboratories, New Brunswick, N.J.

Tumor necrosis factor (α) (TNF)concentration is determined using ELISAkits available from Genzyme, Cambridge, Mass.; R&D Systems, Minneapolis,Minn.; or Pharmingen, San Diego, Calif.

The table below lists the lowest concentration found to induceinterferon and the lowest concentration found to induce tumor necrosisfactor for each compound. A “**” indicates that no induction was seen atany of the tested concentrations (0.12, 0.37, 1.11, 3.33, 10 and 30 μM).A “***” indicates that no induction was seen at any of the testedconcentrations (0.0001, 0.001, 0.01, 0.1, 1 and 10 μM). Unless otherwiseindicated, the interferon biosynthesis was determined by ELISA.

Cytokine Induction in Human Cells Example Lowest Effective Concentration(μM) Number Interferon Tumor Necrosis Factor 1 0.37 10 3 0.37 1.11 40.04 0.37 5 0.04 0.37 6 0.12 1.11 7 1.11 ** 8 0.04 ** 9 0.37 3.33 103.33 ** 11 1.11 ** 12 3.33 ** 13 1.11 3.33 14 3.33 ** 15 3.33 ** 16 1.1130 17 3.33 10 18 3.33 ** 19 10 ** 20 3.33 ** 21 0.12 1.11 22 0.37 10 231.11 ** 24 0.12 3.33 25 3.33 ** 26 0.37 10 27 ** ** 28 0.12 ** 29 0.12** 31 1.11 ** 32 3.33 ** 33 0.37 ** 34 ** 3.33 35 1.11 ** 36 1.11 10 370.37 ** 38 0.12 3.33 39 3.33 ** 40 0.37 30 41 1.11 ** 42 30 3.33 43 0.12** 44 1.11 ** 45 3.33 ** 46 ** 10 68* 1.11 10 69* 0.12 1.11 70* 0.373.33 71* 0.12 3.33 72* 0.37 10 73* 0.37 10 74* 0.37 10 75* 1.11 ** 76*3.33 ** 77* 1.11 10 78* 0.12 10 79* 0.37 ** 80* 1.11 10 81* 3.33 30 82*0.12 10 83* 1.11 ** 84* 0.12 10 85 1.11 10 86 1.11 10 87 3.33 30 88 10** 89 1.11 10 90 3.33 10 91 3.33 ** 92 3.33 ** 93 1.11 30 94 0.04 3.3395 3.33 30 96 0.37 10 97 0.12 3.33 98 1.11 10 99 0.37 3.33 100 10 3.33101 3.33 ** 102 3.33 ** 103 0.37 10 104 ** ** 105 0.12 10 106 3.33 **107 0.12 10 108 0.12 10 109 ** ** 110 1.11 3.33 111 1.11 ** 112 10 **113 3.33 ** 114 1.11 10 115 1.11 30 116 0.37 10 117 3.33 ** 118 1.11 **119 ** ** 120 0.37 ** 121 1.11 ** 122 3.33 ** 123 3.33 ** 124 1.11 3.33125 1.11 ** 126 3.33 ** 127 ** ** 128 3.33 1.11 129 3.33 ** 130 1.11 10131 3.33 ** 132 1.11 3.33 133 3.33 ** 134 0.37 ** 135 0.12 ** 136 1.11** 137 10 ** 138 1.11 ** 139 ** ** 140 1.11 ** 141 0.37 ** 142 3.33 **143 0.12 ** 144 1.11 ** 145 1.11 ** 146 3.33 ** 148 0.01 1 149 0.001 1150 0.001 0.1 151 0.0001 *** 153 0.0001 0.1 154 0.0001 *** 155 0.0001 1155 0.01 0.1 156 0.001 1 158 0.001 1 159 0.01 1 172 0.0001 1 173 0.001 1174 0.001 1 *Interferon determined using the bioassay method

The present invention has been described with reference to severalembodiments thereof. The foregoing detailed description and exampleshave been provided for clarity of understanding only, and no unnecessarylimitations are to be understood therefrom. It will be apparent to thoseskilled in the art that many changes can be made to the describedembodiments without departing from the spirit and scope of theinvention. Thus, the scope of the invention should not be limited to theexact details of the compositions and structures described herein, butrather by the language of the claims that follow.

What is claimed is:
 1. A pharmaceutical composition comprising atherapeutically effective amount of a compound of the formula (I):

wherein R₁ is -alkyl-NR₃—CO—R₄ or -alkenyl-NR₃—CO—R₄ wherein R4 is aryl,heteroaryl, alkyl or alkenyl, each of which may be unsubstituted orsubstituted by one or more substituents selected from the groupconsisting of: -alkyl; -alkenyl; -alkynyl; -(alkyl)₀₋₁-aryl;-(alkyl)₀₋₁-(substituted aryl); -(alkyl)₀₋₁-heteroaryl;-(alkyl)₀₋₁-(substituted heteroaryl); —O-alkyl; —O-(alkyl)₀₋₁-aryl;—O-(alkyl)₀₋₁-(substituted aryl); —O-(alkyl)₀₋₁-heteroaryl;—O-(alkyl)₀₋₁-(substituted heteroaryl); —CO-aryl; —CO-(substitutedaryl); —CO-heteroaryl; —CO-(substituted heteroaryl); —COOH; —CO—O-alkyl;—CO-alkyl; —S(O)₀₋₂-alkyl; —S(O)₀₋₂-(alkyl)₀₋₁-aryl;—S(O)₀₋₂-(alkyl)₀₋₁-(substituted aryl); —S(O)₀₋₂-(alkyl)₀₋₁-heteroaryl;—S(O)₀₋₂-(alkyl)₀₋₁-(substituted heteroaryl); —P(O)(OR₃)₂;—NR₃—CO—O-alkyl; —N₃; -halogen; —NO₂; —CN; -haloalkyl; —O-haloalkyl;—CO-haloalkyl; —OH; —SH; and if R₄ is alkyl or alkenyl, then thesubstituent can also be oxo; or R₄ is

wherein R₅ is an aryl, (substituted aryl), heteroaryl, (substitutedheteroaryl), heterocyclyl or (substituted heterocyclyl) group; R₂ isselected from the group consisting of: -hydrogen; -alkyl; -alkenyl;-aryl; -(substituted aryl); -heteroaryl; -(substituted heteroaryl);-heterocyclyl; -(substituted heterocyclyl); -alkyl-O-alkyl;-alkyl-O-alkenyl; and -alkyl or alkenyl substituted by one or moresubstituents selected from the group consisting of —OH, -halogen;—N(R₃)₂; —CO—N(R₃)₂; —CO—C₁₋₁₀ alkyl; —CO—O—C₁₋₁₀ alkyl; —N₃; -aryl;-(substituted aryl); -heteroaryl; -(substituted heteroaryl);-heterocyclyl; -(substituted heterocyclyl); —CO-aryl; and—CO-heteroaryl; each R₃ is independently selected from the groupconsisting of hydrogen; C₁₋₁₀alkyl-heteroaryl; C₁₋₁₀ alkyl-(substitutedheteroaryl); C₁₋₁₀ alkyl-aryl; C₁₋₁₀ alkyl-(substituted aryl) and C₁₋₁₀alkyl; n is 0 to 4; and each R present is independently selected fromthe group consisting of C₁₋₁₀ alkyl, C₁₋₁₀ alkoxy, halogen andtrifluoromethyl, wherein the substituent(s) of the substituted aryl,heteroaryl, and heterocyclyl groups are independently selected from thegroup consisting of alkyl, alkoxy, alkylthio, hydroxy, halogen,haloalkyl, haloalkylcarbonyl, haloalkoxy, nitro, alkylcarbonyl,alkenylcarbonyl, arylcarbonyl, heteroarylcarbonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocycloalkyl, nitrile,alkoxycarbonyl, alkanoyloxy, alkanoylthio, and, in the case of aheterocyclyl group, oxo; or a pharmaceutically acceptable salt thereof,in combination with a pharmaceutically acceptable carrier.
 2. Thecomposition of claim 1 wherein R₂ is hydrogen.
 3. The composition ofclaim 1 wherein R₂ is selected from the group consisting of hydrogen;alkyl; alkyl-O-alkyl; (alkyl)₀₋₁aryl; and (alkyl)₀₋₁-(substituted aryl).4. The composition of claim 1 wherein R₄ is aryl or heteroaryl that maybe unsubstituted or substituted by one or more substituents selectedfrom the group consisting of: -alkyl; -alkenyl; -alkynyl;-(alkyl)₀₋₁-aryl; -(alkyl)₀₋₁-(substituted aryl);-(alkyl)₀₋₁-heteroaryl; -(alkyl)₀₋₁-(substituted heteroaryl); —O-alkyl;—O-(alkyl)₀₋₁-aryl; —O-(alkyl)₀₋₁-(substituted aryl);—O-(alkyl)₀₋₁-heteroaryl; —O-(alkyl)₀₋₁-(substituted heteroaryl);—CO-aryl; —CO-(substituted aryl); —CO-heteroaryl; —CO-(substitutedheteroaryl); —COOH; —CO—O-alkyl; —CO-alkyl; —S(O)₀₋₂-alkyl;—S(O)₀₋₂-(alkyl)₀₋₁-aryl; —S(O)₀₋₂-(alkyl)₀₋₁-(substituted aryl);—S(O)₀₋₂-(alkyl)₀₋₁-heteroaryl; —S(O)₀₋₂-(alkyl)₀₋₁-(substitutedheteroaryl); —NR₃—CO—O-alkyl; —P(O)(OR₃)₂; —N₃; -halogen; —NO₂; —CN;-haloalkyl; —O-haloalkyl; —CO-haloalkyl; —OH; and —SH.
 5. Thecomposition of claim 1 wherein R₄ is


6. The composition of claim 5 wherein R₅ is 4-pyridyl.
 7. A compoundselected from the group consisting of:N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-ethoxy-1-naphthamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-cyanobenzamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-3-cyanobenzamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-1-naphthamide;N²-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-naphthamide;N¹-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-4-(1-pyrrolyl)benzamide;N¹-{4-(4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl)butyl}-1-naphthamide;N²-{4-(4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl)butyl}-2-naphthamide;N¹-{4-(4-Amino-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-1-yl)butyl}-1-naphthamide;N²-{4-(4-Amino-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-1-yl)butyl}-2-naphthamide;N¹-[4-(4-Amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-1-naphthamide;N²-[4-(4-Amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-naphthamide;N¹-[4-(4-Amino-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-1-naphthamide;andN²-[4-(4-Amino-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-naphthamide.8. A pharmaceutical composition comprising a therapeutically effectiveamount of a compound of the formula (Ib):

wherein R₁ is -alkyl-NR₃—CO—R₄ or -alkenyl-NR₃—CO—R₄ wherein R₄ isheterocyclyl which may be unsubstituted or substituted by one or moresubstituents selected from the group consisting of: -alkyl; -alkenyl;-alkynyl; -(alkyl)₀₋₁-aryl; -(alkyl)₀₋₁-(substituted aryl);-(alkyl)₀₋₁-heterocyclyl; -(alkyl)₀₋₁-(substituted heterocyclyl);-(alkyl)₀₋₁-heteroaryl; -(alkyl)₀₋₁-(substituted heteroaryl); —O-alkyl;—O-(alkyl)₀₋₁-aryl; —O-(alkyl)₀₋₁-(substituted aryl);—O-(alkyl)₀₋₁-heterocyclyl; —O-(alkyl)₀₋₁-(substituted heterocyclyl);—O-(alkyl)₀₋₁-heteroaryl; —O-(alkyl)₀₋₁-(substituted heteroaryl);—CO-aryl; —CO-(substituted aryl); —CO-heteroaryl; —CO-(substitutedheteroaryl); —COOH; —CO—O-alkyl; —CO-alkyl; —S(O)₀₋₂-alkyl;—S(O)₀₋₂-(alkyl)₀₋₁-aryl; —S(O)₀₋₂-(alkyl)₀₋₁-(substituted aryl);—S(O)₀₋₂-(alkyl)₀₋₁-heterocyclyl; —S(O)₀₋₂-(alkyl)₀₋₁-(substitutedheterocyclyl); —S(O)₀₋₂-(alkyl)₀₋₁-heteroaryl;—S(O)₀₋₂-(alkyl)₀₋₁-(substituted heteroaryl); —P(O)(OR₃)₂;—NR₃—CO—O-alkyl; —N₃; oxo; -halogen; —NO₂; —CN; -haloalkyl;—O-haloalkyl; —CO-haloalkyl; —OH; and —SH; or R₄ is

wherein R₅ is an aryl, (substituted aryl), heteroaryl, (substitutedheteroaryl), heterocyclyl or (substituted heterocyclyl) group; R₂ isselected from the group consisting of: -hydrogen; -alkyl; -alkenyl;-aryl; -(substituted aryl); -heteroaryl; -(substituted heteroaryl);-heterocyclyl; -(substituted heterocyclyl); -alkyl-O-alkyl;-alkyl-O-alkenyl; and -alkyl or alkenyl substituted by one or moresubstituents selected from the group consisting of: —OH; -halogen;—N(R₃)₂; —CO—N(R₃)₂; —CO—C₁₋₁₀ alkyl; —CO—O—C₁₋₁₀ alkyl; —N₃; -aryl;-(substituted aryl); -heteroaryl; -(substituted heteroaryl);-heterocyclyl; -(substituted heterocyclyl); —CO-aryl; and—CO-heteroaryl; each R₃ is independently selected from the groupconsisting of hydrogen; C₁₋₁₀ alkyl-heteroaryl; C₁₋₁₀ alkyl-(substitutedheteroaryl); C₁₋₁₀ alkyl-aryl; C₁₋₁₀ alkyl-(substituted aryl) and C₁₋₁₀alkyl; n is 0 to 4; and each R present is independently selected fromthe group consisting of C₁₋₁₀ alkyl, C₁₋₁₀ alkoxy, halogen andtrifluoromethyl, or a pharmaceutically acceptable salt thereof, incombination with a pharmaceutically acceptable carrier.
 9. A compound ofthe formula (Ic):

wherein R₁ is -alkyl-NR₃—CO—R₄ or -alkenyl-NR₃—CO—R₄ wherein R₄ is aryl,heteroaryl, heterocyclyl, alkyl or alkenyl, each of which may beunsubstituted or substituted by one or more substituents selected fromthe group consisting of: -alkyl; -alkenyl; -alkynyl; -(alkyl)₀₋₁-aryl;-(alkyl)₀₋₁-(substituted aryl); -(alkyl)₀₋₁-heteroaryl;-(alkyl)₀₋₁-(substituted heteroaryl); -(alkyl)₀₋₁-heterocyclyl;-(alkyl)₀₋₁-(substituted heterocyclyl); —O-alkyl; —O-(alkyl)₀₋₁-aryl;—O-(alkyl)₀₋₁-(substituted aryl); —O-(alkyl)₀₋₁-heteroaryl;—O-(alkyl)₀₋₁-(substituted heteroaryl); —O-(alkyl)₀₋₁-heterocyclyl;—O-(alkyl)₀₋₁-(substituted heterocyclyl); —CO-aryl; —CO-(substitutedaryl); —CO-heteroaryl; —CO-(substituted heteroaryl); —COOH; —CO—O-alkyl;—CO-alkyl; —S(O)₀₋₂-alkyl; —S(O)₀₋₂-(alkyl)₀₋₁-aryl;—S(O)₀₋₂-(alkyl)₀₋₁-(substituted aryl); —S(O)₀₋₂-(alkyl)₀₋₁-heteroaryl;—S(O)₀₋₂-(alkyl)₀₋₁-(substituted heteroaryl);—S(O)₀₋₂-(alkyl)₀₋₁-heterocyclyl; —S(O)₀₋₂-(alkyl)₀₋₁-(substitutedheterocyclyl); —NR₆—CO—O-alkyl; —P(O)(OR₃)₂; —N₃; -halogen; —NO₂; —CN;-haloalkyl; —O-haloalkyl; —CO-haloalkyl; —OH; —SH; and in the case ofalkyl, alkenyl, or heterocyclyl, oxo; or R₄ is

wherein R₅ is an aryl, (substituted aryl), heteroaryl, (substitutedheteroaryl), heterocyclyl or (substituted heterocyclyl) group; R₂ isselected from the group consisting of: -hydrogen; -alkyl; -alkenyl;-aryl; -(substituted aryl); -heteroaryl; -(substituted heteroaryl);-heterocyclyl; -(substituted heterocyclyl); -alkyl-O-alkyl;-alkyl-O-alkenyl; and -alkyl or alkenyl substituted by one or moresubstituents selected from the group consisting of: —OH; -halogen;—N(R₆)₂; —CO—N(R₆)₂; —CO—C₁₋₁₀ alkyl; —CO—O—C₁₋₁₀ alkyl; —N₃; -aryl;-(substituted aryl); -heteroaryl; -(substituted heteroaryl);-heterocyclyl; -(substituted heterocyclyl); —CO-aryl; and—CO-heteroaryl; R₃ is selected from the group consisting of C₁₋₁₀alkyl-heteroaryl; C₁₋₁₀ alkyl-(substituted heteroaryl); C₁₋₁₀alkyl-aryl; C₁₋₁₀ alkyl-(substituted aryl) and C₁₋₁₀ alkyl; each R₆ isindependently selected from the group consisting of hydrogen; C₁₋₁₀alkyl-heteroaryl; C₁₋₁₀ alkyl-(substituted heteroaryl); C₁₋₁₀alkyl-aryl; C₁₋₁₀ alkyl-(substituted aryl) and C₁₋₁₀ alkyl; n is 0 to 4;and each R present is independently selected from the group consistingof C₁₋₁₀ alkyl, C₁₋₁₀ alkoxy, halogen and trifluoromethyl, wherein thesubstituent(s) of the substituted aryl, heteroaryl, and heterocyclylgroups are independently selected from the group consisting of alkyl,alkoxy, alkylthio, hydroxy, halogen, haloalkyl, haloalkylcarbonyl,haloalkoxy, nitro, alkylcarbonyl, alkenylcarbonyl, arylcarbonyl,heteroarylcarbonyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl, heterocycloalkyl, nitrile, alkoxycarbonyl, alkanoyloxy,alkanoylthio, and, in the case of a heterocyclyl group, oxo; or apharmaceutically acceptable salt thereof.
 10. A compound of claim 9wherein the dashed bonds are absent.
 11. A compound of claim 9 whereinR₃ is selected from the group consisting of C₁₋₁₀ alkyl-heteroaryl;C₁₋₁₀ alkyl-(substituted heteroaryl); C₁₋₁₀ alkyl-aryl; and C₁₋₁₀alkyl-(substituted aryl).
 12. A compound of claim 9 wherein R₃ isselected from the group consisting of C₁₋₁₀ alkyl-heteroaryl; C₁₋₁₀alkyl-(substituted heteroaryl); C₁₋₁₀ alkyl-aryl; C₁₋₁₀alkyl-(substituted aryl) and C₆₋₁₀ alkyl.
 13. A compound of claim 9wherein R₃ is selected from the group consisting of 2-methoxybenzyl;2-furylmethyl; 3-furylmethyl; 2-nitrobenzyl; and 4-pyridylmethyl.
 14. Acompound of claim 13 wherein R₂ is hydrogen and R₄ is methyl.
 15. Acompound of claim 9 wherein n is
 0. 16. A compound of claim 9 wherein R₂is selected from the group consisting of hydrogen; alkyl; alkyl-O-alkyl;(alkyl)₀₋₁ aryl, (alkyl)₀₋₁-(substituted aryl); (alkyl)₀₋₁-heteroaryl;and (alkyl)₀₋₁-(substituted heteroaryl).
 17. A compound of claim 9wherein R₂ is selected from the group consisting of hydrogen; C₁₋₄alkyl; and C₁₋₄alkyl-O—C₁₋₄alkyl.
 18. A compound of claim 9 wherein R₁is —(CH₂)₁₋₆—NR₃—CO—R₄—.
 19. A compound of claim 9 wherein R₄ isnaphthyl that may be unsubstituted or substituted by one or moresubstituents selected from the group consisting of: -alkyl; -alkenyl;-alkynyl; -(alkyl)₀₋₁-aryl; -(alkyl)₀₋₁-(substituted aryl);-(alkyl)₀₋₁-heteroaryl; -(alkyl)₀₋₁-(substituted heteroaryl); —O-alkyl,—O-(alkyl)₀₋₁-aryl; —O-(alkyl)₀₋₁-(substituted aryl);—O-(alkyl)₀₋₁-heteroaryl; —O-(alkyl)₀₋₁-(substituted heteroaryl);—CO-aryl; —CO-(substituted aryl); —CO-heteroaryl; —CO-(substitutedheteroaryl); —CO—O-alkyl; —CO-alkyl; —COOH; —S(O)₀₋₂-alkyl;—S(O)₀₋₂-(alkyl)₀₋₁-aryl; —S(O)₀₋₂-(alkyl)₀₋₁-(substituted aryl);—S(O)₀₋₂-(alkyl)₀₋₁-heteroaryl; —S(O)₀₋₂-(alkyl)₀₋₁-(substitutedheteroaryl); —NR₃—CO—O-alkyl; —P(O)(OR₃)₂; —N₃; oxo; -halogen; —NO₂;—CN; -haloalkyl; —O-haloalkyl; —CO-haloalkyl; —OH; and —SH.
 20. Acompound of the formula (Id):

wherein R₁ is -alkyl-NR₃—CO—R₄ or -alkenyl-NR₃—CO—R₄ wherein R₄ is arylor heteroaryl which may be unsubstituted or substituted by one or moresubstituents selected from the group consisting of: -alkyl; -alkenyl;-alkynyl; -(alkyl)₀₋₁-aryl; -(alkyl)₀₋₁-(substituted aryl);-(alkyl)₀₋₁-heteroaryl; -(alkyl)₀₋₁-(substituted heteroaryl);-(alkyl)₀₋₁-heterocyclyl; -(alkyl)₀₋₁-(substituted heterocyclyl);—O-alkyl; —O-(alkyl)₀₋₁-aryl; —O-(alkyl)₀₋₁-(substituted aryl);—O-(alkyl)₀₋₁-heteroaryl; —O-(alkyl)₀₋₁-(substituted heteroaryl);—O-(alkyl)₀₋₁-heterocyclyl; —O-(alkyl)₀₋₁-(substituted heterocyclyl);—CO-aryl; —CO-(substituted aryl); —CO-heteroaryl; —CO-(substitutedheteroaryl); —CO—O-alkyl; —COOH; —CO-alkyl; —S(O)₀₋₂-alkyl;—S(O)₀₋₂-(alkyl)₀₋₁-aryl; —S(O)₀₋₂-(alkyl)₀₋₁-(substituted aryl);—S(O)₀₋₂-(alkyl)₀₋₁-heteroaryl; —S(O)₀₋₂-(alkyl)₀₋₁-(substitutedheteroaryl); —S(O)₀₋₂-(alkyl)₀₋₁-heterocyclyl;—S(O)₀₋₂-(alkyl)₀₋₁-(substituted heterocyclyl); —NR₃—CO—O-alkyl;—P(O)(OR₃)₂; —N₃; -halogen; —NO₂; —CN; -haloalkyl; —O-haloalkyl;—CO-haloalkyl; —OH; and —SH; or R₄ is

wherein R₅ is an aryl, (substituted aryl), heteroaryl, (substitutedheteroaryl), heterocyclyl or (substituted heterocyclyl) group; R₂ isselected from the group consisting of: -hydrogen; -alkyl; -alkenyl;-aryl; -(substituted aryl); -heteroaryl; -(substituted heteroaryl);-heterocyclyl; -(substituted heterocyclyl); -alkyl-O-alkyl;-alkyl-O-alkenyl; and -alkyl or alkenyl substituted by one or moresubstituents selected from the group consisting of: —OH; -halogen;—N(R₃)₂; —CO—N(R₃)₂; —CO—C₁₋₁₀ alkyl; —CO—O—C₁₋₁₀ alkyl; —N₃; -aryl;-(substituted aryl); -heteroaryl; -(substituted heteroaryl);-heterocyclyl; -(substituted heterocyclyl); —CO-aryl; and—CO-heteroaryl; each R₃ is independently selected from the groupconsisting of hydrogen; C₁₋₁₀ alkyl-heteroaryl; C₁₋₁₀ alkyl-(substitutedheteroaryl); C₁₋₁₀ alkyl-aryl; C₁₋₁₀ alkyl-(substituted aryl) and C₁₋₁₀alkyl; n is 0 to 4; and each R present is independently selected fromthe group consisting of C₁₋₁₀ alkyl, C₁₋₁₀ alkoxy, halogen andtrifluoromethyl, or a pharmaceutically acceptable salt thereof, with theproviso that R₄ is not an unsubstituted benzene ring, and that when R₄is a substituted benzene ring the substituents are selected from thegroup consisting of alkyl, alkoxy, alkylthio, hydroxy, haloalkyl,haloalkylcarbonyl, haloalkoxy, alkylcarbonyl, alkenylcarbonyl,arylcarbonyl, heteroarylcarbonyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocycloalkyl, nitrile,alkoxycarbonyl, alkanoyloxy, alkanoylthio, and—(C₁₋₁₀alkyl)—NR₃—(C₁₋₁₀alkyl)—R₅, wherein R₅ is an aryl, (substitutedaryl), heteroaryl, (substituted heteroaryl), heterocyclyl or(substituted heterocyclyl) group.
 21. A compound of claim 20 wherein nis
 0. 22. A compound of claim 20 wherein R₂ is selected from the groupconsisting of hydrogen; alkyl; alkyl-O-alkyl; (alkyl)₀₋₁aryl; and(alkyl)₀₋₁-(substituted aryl).
 23. A compound of claim 20 wherein R₂ isselected from the group consisting of hydrogen, C₁₋₄ alkyl, andC₁₋₄alkyl-O—C₁₋₄alkyl.
 24. A compound of claim 23 wherein R₂ is hydrogenor methoxyethyl.
 25. A compound of claim 20 wherein R₁ is—(CH₂)₁₋₆—NR₃—CO—R₄—.
 26. A compound of claim 20 wherein R₃ is hydrogen.27. A compound of claim 20 wherein R₄ is naphthyl, quinolinyl,isoquinolinyl or pyridyl that may be unsubstituted or substituted by oneor more substituents selected from the group consisting of: -alkyl;-alkenyl; -alkynyl; -(alkyl)₀₋₁-aryl; -(alkyl)₀₋₁-(substituted aryl);-(alkyl)₀₋₁-heteroaryl; -(alkyl)₀₋₁-(substituted heteroaryl); —O-alkyl;—O-(alkyl)₀₋₁-aryl; —O-(alkyl)₀₋₁-(substituted aryl);—O-(alkyl)₀₋₁-heteroaryl; —O-(alkyl)₀₋₁-(substituted heteroaryl);—CO-aryl; —CO-(substituted aryl); —CO-heteroaryl; —CO-(substitutedheteroaryl); —COOH; —CO—O-alkyl; —CO-alkyl; —S(O)₀₋₂-alkyl;—S(O)₀₋₂-(alkyl)₀₋₁-aryl; —S(O)₀₋₂-(alkyl)₀₋₁-(substituted aryl);—S(O)₀₋₂-(alkyl)₀₋₁-heteroaryl; —S(O)₀₋₂-(alkyl)₀₋₁-(substitutedheteroaryl); —NR₃—CO—O-alkyl; —P(O)(OR₃)₂; —N₃; -halogen; —NO₂; —CN;-haloalkyl; —O-haloalkyl; —CO-haloalkyl; —OH; and —SH.
 28. A compound ofclaim 27 wherein: R₂ is selected from the group consisting of hydrogen;alkyl; alkyl-O-alkyl; (alkyl)₀₋₁aryl; and (alkyl)₀₋₁-(substituted aryl);R₃ is hydrogen; and n is
 0. 29. A compound of the formula (Ie):

wherein R₁ is -alkyl-NR₃—CO—R₄ or -alkenyl-NR₃—CO—R₄ wherein R₄ is analkyl or alkenyl group that is substituted by one or more substituentsselected from the group consisting of: -alkynyl; -(substituted aryl)wherein the substituent(s) is selected from the group consisting ofalkyl, alkoxy, alkylthio, hydroxy, haloalkyl, haloalkylcarbonyl,haloalkoxy, alkylcarbonyl, alkenylcarbonyl, arylcarbonyl,heteroarylcarbonyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl, heterocycloalkyl, nitrile, alkoxycarbonyl, alkanoyloxy,and alkanoylthio; -heteroaryl; -(substituted heteroaryl); —O-alkyl;—O-(alkyl)₀₋₁-(substituted aryl) wherein the substituent(s) is selectedfrom the group consisting of alkyl, alkoxy, alkylthio, hydroxy,haloalkyl, haloalkylcarbonyl, haloalkoxy, alkylcarbonyl,alkenylcarbonyl, arylcarbonyl, heteroarylcarbonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocycloalkyl, nitrile,alkoxycarbonyl, alkanoyloxy, and alkanoylthio; —O-(alkyl)₀₋₁-heteroaryl;—O-(alkyl)₀₋₁-(substituted heteroaryl); —CO-aryl; —CO-(substitutedaryl); —CO-heteroaryl; —CO-(substituted heteroaryl); —COOH; —CO—O-alkyl;—CO-alkyl; —S(O)₀₋₂-alkyl; —S(O)₀₋₂-(alkyl)₀₋₁-aryl;—S(O)₀₋₂-(alkyl)₀₋₁-(substituted aryl); —S(O)₀₋₂-(alkyl)₀₋₁-heteroaryl;—S(O)₀₋₂-(alkyl)₀₋₁-(substituted heteroaryl); —NR₃—CO—O-alkyl;—P(O)(OR₃)₂; —N₃; oxo; —NO₂; —CN; —O-haloalkyl; —CO-haloalkyl; —OH; and—SH; R₂ is selected from the group consisting of: -hydrogen; -alkyl;-alkenyl; -aryl; -(substituted aryl); -heteroaryl; -(substitutedheteroaryl); -heterocyclyl; -(substituted heterocyclyl); -alkyl-O-alkyl; -alkyl-O-alkenyl; and -alkyl or alkenyl substituted by one ormore substituents selected from the group consisting of: —OH; -halogen;—N(R₃)₂; —CO—N(R₃)₂; —CO—C₁₋₁₀ alkyl; —N₃; -aryl; -(substituted aryl);-heteroaryl; -(substituted heteroaryl); -heterocyclyl; -(substitutedheterocyclyl); —CO-aryl; and —CO-heteroaryl; each R₃ is independentlyselected from the group consisting of hydrogen; C₁₋₁₀ alkyl-heteroaryl;C₁₋₁₀ alkyl-(substituted heteroaryl); C₁₋₁₀ alkyl-aryl; C₁₋₁₀alkyl-(substituted aryl) and C₁₋₁₀ alkyl; n is 0 to 4; and each Rpresent is independently selected from the group consisting of C₁₋₁₀alkyl, C₁₋₁₀ alkoxy, halogen and trifluoromethyl, or a pharmaceuticallyacceptable salt thereof.
 30. A compound of claim 29 wherein n is
 0. 31.A compound of claim 29 wherein R₂ is selected from the group consistingof hydrogen, alkyl, alkyl-O-alkyl, (alkyl)₀₋₁-aryl, and(alkyl)₀₋₁-(substituted aryl).
 32. A compound of claim 29 wherein R₂ isselected from the group consisting of hydrogen, C₁₋₄ alkyl, andC₁₋₄alkyl-O—C₁₋₄alkyl.
 33. A compound of claim 29 wherein R₂ is hydrogenor methoxyethyl.
 34. A compound of claim 33 wherein n is
 0. 35. Acompound of claim 33 wherein R₃ is hydrogen and n is
 0. 36. A compoundof claim 29 wherein R₃ is hydrogen.
 37. A pharmaceutical compositioncomprising a therapeutically effective amount of a compound selectedfrom the group consisting of:N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamide;N¹-[4-(4-Amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamide;N¹-[4-(4-Amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamide;N¹-[4-(4-Amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamide;N¹-[4-(4-Amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamide;N¹-[5-(4-Amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)pentyl]benzamide;N¹-[5-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)pentyl]benzamide;N¹-[3-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)propyl]benzamide;N¹-[2-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]benzamide;N¹-[3-(4-Amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]benzamide;N¹-[6-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)hexyl]benzamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-3-phenylpropanamide;N¹-[2-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-3-phenylpropanamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-phenoxyacetamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-ethylhexanamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-phenoxypropanamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-chlorobenzamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-3,4-dichlorobenzamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2,6-dichlorobenzamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-fluorobenzamnide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-chlorobenzamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-methoxybenzamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-(trifluoromethyl)benzamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-phenylacetamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-(E)-3-phenyl-2-propenamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-3-cyclopentylpropanamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-1-cyclopentanecarboxamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-1-cyclohexanecarboxamide;N¹-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-2-methylbenzamide;N¹-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-1-cyclopentanecarboxamide;N¹-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-1-cyclohexanecarboxamide,N¹-{4-[4-Amino-2-(2-methoxyethyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-1-yl]butyl}benzamide;N¹-{4-[4-Amino-2-(2-methoxyethyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-2-phenylacetamide;N¹-[4-(4-Amino-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-1-yl)butyl]acetamide;N¹-[4-(4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl)butyl]acetamide;N¹-[4-(4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2,2,2trifluoroacetamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2,2,2-trifluoroacetamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-(trans)-2-phenylcyclopropane-1-carboxamide;andN¹-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-(trans)-2-phenylcyclopropane-1-carboxamidein combination with a pharmaceutically acceptable carrier.
 38. Acompound selected from the group consisting of:N⁶-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-quinolinecarboxamide;N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-3-quinolinecarboxamide;N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2,6-dimethoxynicotinamide;N⁸-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-8-quinolinecarboxamide;N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]nicotinamide;N⁴-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]isonicotinamide;N⁴-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-quinolinecarboxamide;N⁴-[4-(4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-phenyl-4-quinolinecarboxamide;N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-(pentylsulfanyl)nicotinamide;N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-cyanonicotinamide;N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-chloronicotinamide;N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-(2,2,2-trifluoroethoxy)nicotinamide;N²-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-2-quinolinecarboxamide;N¹-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-1-isoquinolinecarboxamide;N²-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-5-butyl-2-pyridinecarboxamide;N³-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-3-indolecarboxamide;N²-{4-[4-Amino-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-2-quinolinecarboxamide;N³-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-6-(1-pyrrolyl)nicotinamide;N⁵-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-5-indolecarboxamide;N³-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-5-(2-phenyl-1-ethynyl)nicotinamide;N³-[4-(4-Amino-2-phenyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]nicotinamide;N²-[4-(4-Amino-2-phenyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-quinolinecarboxamide;N³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-chloronicotinamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-(2-thienyl)acetamide;N¹-[4-(4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-(3thienyl)acetamide;N²-{4-[4-Amino-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-2-pyridinecarboxamide;N³-{4-[4-Amino-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-nicotinamide;N⁴-{4-[4-Amino-2-(2-methoxyethyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-1-yl]butyl}isonicotinamide;N³-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-3-furamide;N³-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}nicotinamide;N²-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-furamide;N²-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-thiophenecarboxamide;andN²-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-5-nitro-2-furamide.39. A compound selected from the group consisting of:N¹-[4-(4-Amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentanamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentanamide;N¹-[2-(4-Amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-5-(2-iminoperhydrothieno[3,4-d]imidazol-4-yl)pentanamide;N¹-[2-(4-Amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentanamide;andN¹-[2-(4-Amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentanamide.40. A compounds selected from the group consisting of:N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-(morpholinomethyl)benzamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-{[(4-pyridylmethyl)amino]methyl}benzamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-{[(2-methoxyphenethyl)amino]methyl}benzamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-({methyl[2-(2-pyridyl)ethyl]amino}methyl)benzamide;N¹-{4-[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-2-oxo-2-phenylacetamide;N¹-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-[(2-tetrahydro-1H-1-pyrrolyl-1H-benzo[d]imidazol-1-yl)methyl]benzamide;andN³-[4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-6-morpholinonicotinamide.41. A compound selected from the group consisting of:N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(4-methoxybenzyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(4-bromobenzyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(5-bromo-2-hydroxybenzyl)-acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(4-butoxybenzyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(2-chlorobenzyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(2-chloro-5-nitrobenzyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(5-chloro-2-nitrobenzyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-2-[(4-chlorophenyl)sulfanyl]benzylacetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(3,5-dichlorobenzyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(3,4-difluorobenzyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(2,5-dimethoxybenzyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(2,3-dimethoxybenzyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(2,4-dimethylbenzyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-[(5-ethyl-2-furyl)methyl]acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(2-furylmethyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(3-furylmethyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(3-phenylpropyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-octylacetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(1-naphthylmethyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-[(2-methoxy-1naphthylmethyl]acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(4-nitrobenzyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(2-nitrobenzyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(4-pyridylmethyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(2-methylbenzyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(2,3,4-trimethoxybenzyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(3,4,5-trimethoxybenzyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-cyclopentylacetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-(4-fluorophenyl)acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-isopropylacetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-[4-(trifluoromethyl)phenyl]acetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-cyclohexylmethylacetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-benzylacetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-methylacetamide;N¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-ethylacetamide;andN¹-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N¹-benzyl-2,2,2-trifluoroacetamide.42. A pharmaceutical composition comprising a therapeutically effectiveamount of a compound of claim 9 in combination with a pharmaceuticallyacceptable carrier.
 43. A pharmaceutical composition comprising atherapeutically effective amount of a compound of claim 20 incombination with a pharmaceutically acceptable carrier.
 44. Apharmaceutical composition comprising a therapeutically effective amountof a compound of claim 29 in combination with a pharmaceuticallyacceptable carrier.
 45. A method of inducing cytokine biosynthesis in ananimal comprising administering an effective amount of a composition ofclaim 1 to the animal.
 46. A method of treating a viral disease in ananimal comprising administering an effective amount of a composition ofclaim 1 to the animal.
 47. A method of treating a neoplastic disease inan animal comprising administering an effective amount of a compositionof claim 1 to the animal.
 48. A method of inducing cytokine biosynthesisin an animal comprising administering an effective amount of acomposition of claim 8 to the animal.
 49. A method of treating a viraldisease in an animal comprising administering an effective amount of acomposition of claim 8 to the animal.
 50. A method of treating aneoplastic disease in an animal comprising administering an effectiveamount of a composition of claim 8 to the animal.
 51. A method ofinducing cytokine biosynthesis in an animal comprising administering aneffective amount of a compound of claim 9 to the animal.
 52. A method oftreating a viral disease in an animal comprising administering aneffective amount of a compound of claim 9 to the animal.
 53. A method oftreating a neoplastic disease in an animal comprising administering aneffective amount of a compound of claim 9 to the animal.
 54. A method ofinducing cytokine biosynthesis in an animal comprising administering aneffective amount of a compound of claim 20 to the animal.
 55. A methodof treating a viral disease in an animal comprising administering aneffective amount of a compound of claim 20 to the animal.
 56. A methodof treating a neoplastic disease in an animal comprising administeringan effective amount of a compound of claim 20 to the animal.
 57. Amethod of inducing cytokine biosynthesis in an animal comprisingadministering an effective amount of a compound of claim 29 to theanimal.
 58. A method of treating a viral disease in an animal comprisingadministering an effective amount of a compound of claim 29 to theanimal.
 59. A method of treating a neoplastic disease in an animalcomprising administering an effective amount of a compound of claim 29to the animal.
 60. A pharmaceutical composition comprising atherapeutically effective amount of a compound of the formula (Ia):

wherein R₁ is -alkyl-NR₃—CO—R₄ or -alkenyl-NR₃—CO—R₄ wherein R₄ is aryl,heteroaryl, alkyl or alkenyl, each of which may be unsubstituted orsubstituted by one or more substituents selected from the groupconsisting of: -heterocyclyl; -(substituted heterocyclyl);-(alkyl)₀₋₁heterocyclyl; -(alkyl)₀₋₁(substituted heterocyclyl);—O-(alkyl)₀₋₁heterocyclyl; —O-(alkyl)₀₋₁(substituted heterocyclyl);—S(O)₀₋₂-(alkyl)₀₋₁heterocyclyl; and —S(O)₀₋₂-(alkyl)₀₋₁(substitutedheterocyclyl); R₂ is selected from the group consisting of: -hydrogen;-alkyl; -alkenyl; -aryl; -(substituted aryl); -heteroaryl; -(substitutedheteroaryl); -heterocyclyl; -(substituted heterocyclyl); -alkyl-O-alkyl;-alkyl-O-alkenyl; and -alkyl or alkenyl substituted by one or moresubstituents selected from the group consisting of: —OH; -halogen;—N(R₃)₂; —CO—N(R₃)₂; —CO—C₁₋₁₀ alkyl; —CO—O—C₁₋₁₀ alkyl; —N₃; -aryl;-(substituted aryl); -heteroaryl; -(substituted heteroaryl);-heterocyclyl; -(substituted heterocyclyl); —CO-aryl; and—CO-heteroaryl; each R₃ is independently selected from the groupconsisting of hydrogen; C₁₋₁₀ alkyl-heteroaryl; C₁₋₁₀ alkyl-(substitutedheteroaryl); C₁₋₁₀ alkyl-aryl; C₁₋₁₀ alkyl-(substituted aryl) and C₁₋₁₀alkyl; n is 0to 4; and each R present is independently selected from thegroup consisting of C₁₋₁₀ alkyl, C₁₋₁₀ alkoxy, halogen andtrifluoromethyl, or a pharmaceutically acceptable salt thereof, incombination with a pharmaceutically acceptable carrier.
 61. A method ofinducing cytokine biosynthesis in an animal comprising administering aneffective amount of a composition of claim 60 to the animal.
 62. Amethod of treating a viral disease in an animal comprising administeringan effective amount of a composition of claim 60 to the animal.
 63. Amethod of treating a neoplastic disease in an animal comprisingadministering an effective amount of a composition of claim 60 to theanimal.
 64. The composition of claim 60 wherein R₄ is

and X is O, S, or NH.